Integrating microbial fermentation and polymerization for sustainable polylactic acid production

Abstract

Abstract

Replacing petroleum-based plastics with sustainable alternatives requires economically viable biomanufacturing routes. This review comprehensively assimilates two critical pillars of bio-based polymer development: the microbial synthesis of lactic acid (LA) and its subsequent polymerization into polylactic acid (PLA). The first section critically examines advancements in the eco-friendly production of LA from renewable substrates through microbial fermentation. It highlights recent breakthroughs in metabolic engineering, process optimization, and cleaner downstream purification techniques to achieve high optical purity and yield. The second section focuses on the conversion of LA into PLA, detailing synthesis mechanisms via direct condensation and ring-opening polymerization (ROP). The manuscript evaluates the intricate relationships between PLA’s structural, thermal, and mechanical properties, alongside state-of-the-art processing technologies such as 3D/4D printing and electrospinning. By addressing prevailing bottlenecks—specifically the high cost of raw materials and the precise control of degradation rates—this review provides a strategic roadmap for the sustainable, large-scale production of PLA, aligning bio-based polymer development with shifting environmental and commercial demands.

Key points

• Microbial routes boost sustainable, high-purity lactic acid production.

• Advances in PLA polymerization enhance material performance and applications.

• Lignocellulosic biomass enables low-cost, eco-friendly LA and PLA production.

Supplementary information

The online version contains supplementary material available at https://doi.org/10.1007/s00253-026-13935-6.

Introduction

The lactic acid (LA) market is experiencing significant growth owing to its comprehensive applications as a sustainable platform chemical, driving its worldwide market value toward an estimated USD 9.8 billion by 2025 (Acedos et al. 2022). LA has a stereocenter, resulting in two enantiomers: levorotatory isomer, L-lactic acid (L-LA), and dextrorotatory isomer, D-lactic acid (D-LA). Various microorganisms generate L-LA as a primary fermentative end-product following the reduction of glycolysis-derived pyruvate. From a commercial standpoint, the optical purity of the LA monomer is critical for both food safety and polymer synthesis (Zhou and Hua 2025). The L-LA isomer is preferred for food-contact applications because the human body efficiently metabolises it, leading to favorable regulatory approval and GRAS (generally recognized as safe) status. Conversely, high accumulation of the D-LA isomer can lead to metabolic issues like D-lactic acidosis. In polymer manufacturing, controlling the ratio of L- and D-monomers is equally vital, as blending pure poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA) forms a stereocomplex with superior thermal stability and mechanical properties L-LA and its derivatives are broadly applied in the food sector as acidulants, antimicrobial agents, emulsifying compounds, and preservatives (Ren et al. 2025). Additionally, both L-LA and D-LA serve as essential precursors for polylactic acid (PLA) synthesis, yielding a biodegradable and biocompatible polymer that ultimately breaks down into its constituent lactic acid monomers. PLA is highly suitable for biomedical applications due to its biodegradability, biocompatibility, and favorable physicochemical properties, making it widely applicable in drug delivery systems, absorbable sutures, and tissue engineering The production of optically pure L(+) or D(-) LA is very important for PLA synthesis, as enantiomeric purity decides the crystallinity and mechanical properties of finally synthesized PLA. Fermentation processes can be precisely custom-made to achieve the expected isomer. Consequently, high-purity L-LA is preferred for synthesizing PLA intended for biomedical (Singhvi et al. 2019) and food-contact (Zhou and Hua 2025) applications. Because PLA implants and packaging degrade via hydrolysis into their constituent monomers, the use of L-LA ensures that any released degradation products can be safely metabolised by animal cells without the risk of D-lactic acidosis Hence, the explicit use of LA (L(+) or D(−)) is a crucial factor in monitoring the characteristics of final PLA product and safety profile for various applications.

Lactic acid (LA) production can be achieved either through chemical synthesis or microbial fermentation (Joshi et al. 2010; Singhvi et al. 2019) as depicted in Fig. 1. Industrial chemical synthesis primarily relies on the petrochemical-route hydrolysis of lactonitrile using acetaldehyde and hydrogen cyanide precursors under high-pressure conditions. However, chemical methods inherently generate optically inactive racemic mixtures containing an equal blend of both L(+) and D(−) isomers (Zu et al. 2024), which limits their utility in manufacturing high-tensile polylactic acid (PLA) polymers. Furthermore, this fossil-fuel-dependent pathway poses severe environmental alarms due to the utilization of toxic raw materials and the generation of hazardous chemical byproducts. On the contrary, biological methods currently accounting for 90% of total global LA production are preferred, attributable to their eco-friendly nature and their ability to produce optically pure L(-) or D(-) LA variants with high stereospecific yields (Zhou et al. 2024). Different types of microbes, including bacteria, yeast, fungi, molds, and algae, are utilized in these fermentation-based processes.

Fig. 1.

Comparative LA production by using chemical and biological methods (Singhvi et al. 2019)

While the L-LA industry is rapidly intensifying, current production levels still fall short of meeting the growing global demand. Technoeconomic analyses (TEAs) in recent literature highlight that this economic shortfall is chiefly driven by the high cost of refined, food-grade sugar substrates (such as glucose and sucrose) and fastidious nutrient supplements (like yeast extract), which collectively account for up to 40% of total operating expenses. While transitioning to second-generation lignocellulosic biomass reduces raw material costs, TEAs reveal that intensive chemical and enzymatic pretreatment steps heavily inflate the initial capital expenditure. Beyond upstream costs, downstream processing (DSP) represents the most formidable technical and economic hurdle, often commanding over 50% of total production expenditures. The high hydrophilicity and low volatility of LA render direct thermal distillation inefficient. Consequently, isolating polymer-grade LA from complex fermentation broths—which are laden with residual sugars, cell debris, and metabolic colorants—necessitates capital-intensive purification trains involving sequential microfiltration, ion exchange, and esterification-distillation loops. The increasing production and accumulation of billions of tons of petroleum-based plastics have triggered a global environmental crisis, contributing to greenhouse gas (GHG) emissions. This emphasizes the imperative prerequisite for sustainable and eco-friendly substitutes derived from renewable resources (Al-khairy et al. 2022). Amongst numerous bioplastics, PLA has arisen as a leading contender over conventional plastics like polyethylene terephthalate (PET) and polystyrene (PS) due to its biocompatibility, mechanical properties, and industrial compostability. However, unlike some bio-polymers, PLA requires specific industrial composting facilities to degrade and is not suitable for home composting (Al-khairy et al. 2022). LA, a key precursor required for PLA synthesis, is mainly produced by microbial fermentation processes, which provide a sustainable substitute to conventional chemical methods. Furthermore, chemical methods generate unwanted racemic mixtures of LA. The valorization of profusely obtainable lignocellulosic biomass (LCB) materials as feedstocks for LA production offers a potential approach to encounter waste administration difficulties, though concurrently producing a bio-based, high-value product (Singhvi and Gokhale 2013). This review critically examines recent advances in the field, sustainable approaches, technological obstacles, and future outlooks in the bioconversion of LCB substrates into LA using fermenter-based systems, emphasizing their role in the production of sustainable PLA.

PLA was first revealed by Wallace Carothers (1932), who attained low molecular weight PLA by desiccating LA through heat treatment under vacuum (Holten 1971) Notably, PLA is a prominent commercial linear aliphatic polyester that features high biocompatibility, a bio-based source, and industrial compostability. While other biopolyesters like polyhydroxyalkanoates (PHAs) are also biosynthesized at scale and offer home compostability, PLA remains a market leader due to its established production infrastructureWhile neat PLA exhibits moderate resistance to UV-induced yellowing compared to select petroleum-based polymers, it lacks inherent antibacterial properties and requires specific additives or surface modifications to achieve antimicrobial functionality. (Shi et al. 2024). Also, low molecular weight PLA is usually used in the medical field due to its rapid degradation rate and ability to simplify drug release, while high molecular weight PLA has substantial commercial worth in the fiber, textile, plastic, and packaging sectors (Wu et al. 2024).

The present article provides a detailed investigation of contemporary inventions in the production of LA using renewable materials. It also discovers advances in microbial strain engineering, bioprocess optimization, and downstream methods intended to increase L-LA yield and purity. Eventually, this review underlines promising strategies for the sustainable and economical production of LA and PLA from renewable biological resources.

Different substrates used for lactic acid fermentation

Presently, the production of LA at an industrial scale relies heavily on the utilization of 1st-generation (1G) substrates, which are typically resources of relevance for human nutrition, such as corn, sugarcane, and starch. The widespread use of edible crops for commercial production of LA has, however, sparked crucial debate regarding “food versus fuel” competition, land usage, and global sustainability (Komesu et al. 2017). The abundance and compositional diversity of these substrates provide flexibility in designing and improving fermentation processes. Among the existing substrates, corn starch has arisen as the most commonly used substrate owing to its high amylose and amylopectin content, which serve as efficient carbohydrate sources. Enzymatic hydrolysis can readily convert corn starch into simple sugar, glucose, a favored carbon source for lactic acid bacteria (LAB). Similarly, sucrose-rich sugarcane and sugar beet feedstocks can be hydrolyzed into fermentable monosaccharides via acid hydrolysis or microbial enzymatic reactions (Mabia et al. 2025). While various agro-industrial byproducts like dairy whey represent viable second-generation streams, this section focuses specifically on the conversion of lignocellulosic feedstocks, detailing the distinct pretreatment and sugar-cofermentation challenges inherent to biomass matrix degradation.

Lactic acid (LA) production traditionally relies on first-generation, sugar- and starch-based substrates (such as sugarcane molasses and corn starch) due to their easily fermentable carbohydrate profiles. However, to mitigate the “food vs. fuel” conflict, recent research has pivoted toward non-food alternatives, primarily lignocellulosic biomass (LCB). Nowadays, the research studies highlight the shift from 1st-generation substrates (1G) like corn to sustainable, non-food 2nd-generation substrates (2G) for LA production owing to concerns about competition with food supply chains and land usage (Abdel-Rahman et al. 2011). LCB materials, mainly composed of cellulose, hemicellulose, and lignin, represent an enormous and underutilized biomass resource for LA production. Common agricultural residues such as rice straw, wheat straw, sugarcane bagasse, and corn stover have proved strong potential as substrates for LA production through microbial fermentation (Singhvi et al. 2010). Also, dedicated energy crops, including poplar, giant reed, elephant grass, willow along with industrial by-products such as brewer’s spent grain, whey and paper mill sludge, are being gradually explored for sustainable and cost-effective LA production (Zhang et al. 2020; Kadier et al. 2021). The inherent resistance to degradation, referred to as LCB recalcitrance, requires rigorous and costly pretreatment steps to expose the carbohydrate moieties to enzyme attack (Singhvi et al. 2014). Conversely, starch-based substrates offer a lucrative, renewable, and easily degradable carbon source for microbial fermentation. The amylose and amylopectin fractions in starch are significantly more amenable towards enzymatic attack than the rigid lignin–cellulose moieties in LCB substrates. Hence, no harsh pretreatment steps are required during starch hydrolysis, which ultimately lowers the total energy requirements (Kacaribu and Darwin 2024). The economic viability of LCB depends on overcoming its inherent matrix recalcitrance. Rather than cellulose itself being resistant to processing, the challenge lies in the complex, cross-linked network where crystalline cellulose microfibrils are embedded within a hydrophobic lignin and hemicellulose matrix. Consequently, modern biorefineries utilize targeted pretreatment methods to fractionate and separate the protecting lignin barrier. Once isolated, the remaining cellulose and hemicellulose fractions can be efficiently saccharified into monomeric hexose and pentose sugar feedstocks using advanced enzymatic cocktails or chemical hydrolysis.

Current studies reveal successful LA production by using various 2G substrates and microbial strains, including Pediococcus acidilactici fermenting corn stover, a mixed consortium using sugarcane molasses, Lactobacillus pentosus on food waste, and Bacillus coagulans utilizing corn cob residue (Zhang et al. 2020; Lobeda et al. 2022).

In LCB materials, cellulose and hemicellulose serve as budding sources of fermentable simple sugars. The pretreatment step is necessary to overcome the rigidity of the plant cell wall structure, which helps in improving the enzymatic hydrolysis efficiency of LCB substrates for LA production. Although the pretreatment process increases sugar yields, it also poses challenges such as augmented process complexity and higher capital costs (Solarte-Toro et al. 2019). Furthermore, harsh pretreatment environments may generate inhibitory compounds that deter microbial growth or cause irreversible cellular damage (Baksi et al. 2023). Consequently, the development of environmentally sustainable and cost-effective strategies for 2G substrates biorefining remains a serious research emphasis. A consolidated overview of 2G feedstocks used for LA production is displayed in Table S1. Figure 2 illustrates the process flow of stepwise LCB conversion into LA.

Fig. 2.

Lactic acid production from second-generation biomass substrates through microbial fermentation process

Pretreatment methods are generally categorized into physical, chemical, physical-chemical, and biological methods, albeit with discrete advantages and disadvantages as presented in Fig. 3. Chemical pretreatment processes, demonstrated by acid hydrolysis, efficiently dissolve hemicellulose which can lead to higher LA titers. However, the chemical method often produces fermentation inhibitor compounds and also requires specific corrosion-resistant equipment, which leads to increasing operational costs (Kululo et al. 2025). Ionic liquids (ILs) have emerged as a potential alternative due to their better stability, tunable solubility, low volatility, and recyclability, with reported lignocellulose digestion rates reaching as high as 99.23% (Yang et al. 2022).

Fig. 3.

Advantages and disadvantages of various pretreatment methods for conversion of lignocellulosic biomass substrates

Physical pretreatment drives to curtail chemical usage and waste dumping, using techniques such as milling, grinding, steam explosion, and so on. These methods disrupt the structure of LCB substrates physically/mechanically, hence tumbling chemical agents and by-product formation. For instance, physical pretreatment of sweet sorghum yielded 94 g/L of L-LA (Yan et al. 2024). Nevertheless, physical processes alone are often inadequate and naturally necessitate amalgamation with chemical methods to advance its accessibility towards enzymatic hydrolysis. A collective approach including physical and chemical methods—such as treating dried corn stover with H₂SO₄ and exposing it to steam at high temperature (175 °C) for 5 min, which yielded about one ton of L-LA from 2.87 tons of corn stover, even if with high energy and equipment costs (Esquivel-Hernández et al. 2022).

Biological pretreatment methods employ microbes/enzymes under mild conditions, which condense the generation of inhibitors, lesser use of chemicals, and reduction in energy consumption. and soft rot fungi can degrade cellulose, hemicellulose, and lignin, while brown rot fungi primarily target cellulose and hemicellulose. However, the slow rate of lignin degradation confines industrial scalability. At the commercial level, enzyme cocktails are mostly produced by fungi such as Trichoderma reesei and Aspergillus sp., used in enzymatic hydrolysis. The enzyme production must be performed under sterile conditions to prevent sugar consumption by endogenous microbes (Wan Mohtar et al. 2022). Unlike chemical and physical methods, the biological approach avoids inhibitory by-products, enhances sustainability, but usually comprises higher costs due to enzyme production and purification steps.

The inadequate enzyme productivity of fungi remains a substantial blockade to their wider applications in the valorization of agricultural waste for the production of value-added products. Mutagenesis methods have been broadly employed to boost cellulase yields in fungal strains through genetic modification. A classic example is the development of T. reesei RUT-C30 from the parental strain T. reesei Qm6a via a process of random mutagenesis using UV light and chemical mutagens such as N-methyl-N′-nitro-N-nitrosoguanidine (NTG); this led to a hyper-cellulolytic mutant exhibiting a remarkable 20-fold increase in cellulase activity (Montenecourt and Eveleigh 1977). Such studies highlight the efficiency of both physical and chemical random mutagenesis in fungal strains with dramatically enhanced enzymatic properties for industrial applications.

One prominent strategy encompasses the modification of vital transcriptional regulators. For example, in T. reesei, deletion of the gene encoding the main transcriptional repressor, ACE1, resulted in a mutant strain (T. reesei RUT-C30Δzface1) with significantly improved cellulolytic activities (up to 3.2-fold using Avicel as a substrate) due to alleviation in repression of cellulase genes (Liu et al. 2019). On the other hand, overexpression of positive regulators, such as Xylanase regulator 1 (XYR1), has also led to enhanced enzyme production (Yang et al. 2023). An alternative effective approach is the optimization of the enzyme cocktail by acquainting with or overexpressing specific components that are indeed limiting in the host organism. T. reesei usually secretes low levels of β-glucosidase (BGL) enzymes, which can hamper the inclusive efficacy of LCB substrates hydrolysis. Genetically engineering overexpression of the invertase gene from A. niger into T. reesei was carried out, which enabled the fungus to grow profusely on cheaper substrates like sugarcane molasses (Gao et al. 2017). Similarly, the heterologous expression of lytic polysaccharide monooxygenases (LPMOs) from other fungi, such as Thermoascus aurantiacus in T. reesei has been revealed to augment the overall hydrolytic efficiency of LCB substrates. Additionally, the advancement of genome editing tools, such as the CRISPR-Cas9 system, has revolutionized strain improvement efforts by enabling accurate and precise gene manipulation (e.g., gene deletion or insertion) in several fungal species, including T. reesei and A. niger (Yang et al. 2023). This consents for multi-gene engineering strategies, such as the disruption of non-homologous end-joining pathways to increase the efficiency of targeted gene integration, leading to hyper-producing industrial strains.

Microbes used for lactic acid production

Mostly, wild-type microbial strains are extremely valuable natural producers with vital potential for commercial applications attributable to their integral metabolic strength. Among these, lactic acid bacteria (LAB), yeast, molds, and microalgae have been broadly considered for their capability to produce LA. Lactic acid bacteria (LAB) are Gram-positive micro-organisms capable of converting various carbon substrates into lactic acid. However, their industrial application is severely bottlenecked by product-induced inhibition, as the accumulation of free organic acids rapidly deactivates wild-type strains. To sustain metabolic activity, commercial operations must continuously add neutralizing bases (e.g., Ca(OH)₂ or NaOH), keeping the pH near neutral. A major consequence of this neutralization is the inevitable generation of gypsum (CaSO₄) during subsequent acidification stages in downstream processing (DSP). The accumulation of gypsum poses a severe operational hurdle, complicating downstream purification, driving up waste management costs, and significantly reducing the overall environmental sustainability of the biorefinery process. (Singhvi et al. 2015; Singhvi et al. 2018). To bypass the gypsum loop completely, recent research has intensively focused on acid-tolerant yeast platforms (Zhang et al. 2023). Unlike bacteria, yeast strains such as Saccharomyces cerevisiae, Pichia pastoris, and Pichia kudriavzevii possess robust cell walls and active proton-pumping mechanisms that allow them to thrive in low-pH environments (pH < 4.0) (Altvater et al. 2025). Since these yeasts do not natively produce high yields of lactic acid, metabolic engineering strategies specifically the heterologous expression of lactate dehydrogenase (\(LDH\)) genes paired with the disruption of native pyruvate decarboxylase (PDC\)) genes are deployed (Jang et al. 2021). These engineered yeast strains efficiently accumulate free lactic acid below its pKa threshold, allowing direct downstream recovery without the need for neutralizing agents (Altvater et al. 2025). Beyond bacteria and yeasts, filamentous fungi, notably Rhizopus oryzae, offer an alternative pathway. They can natively utilize complex pentose and hexose sugar streams without demanding expensive organic nitrogen supplements. However, their filamentous morphology increases broth viscosity, which impairs oxygen transfer and reduces overall volumetric productivity compared to bacterial and yeast systems (Akter et al. 2025).

Critical factors impacting the titers of LA production include strain-specific traits, optimized fermentation parameters such as temperatures (45–55 °C), pH levels (5.5–6.5), and suitable nutrient accessibility. Numerous studies have explored the different Lactobacillus strains for LA production from waste materials. For instance, Nagarajan et al. (Nagarajan et al. 2020) reported 33.8 g/L of L-LA production using L. plantarum and coffee waste during the anaerobic fermentation process. Bacillus subtilis was employed for starch hydrolysis followed by fermentation with L. plantarum TD175 strain, which generated a maximum 50.77 g/L of L-LA production from food waste. Additionally, a distinct study carried out a fed-batch fermentation using food waste hydrolysate through Lactobacillus strain which yielded 157.0 g/L of L-LA with the productivity of 2.0 g/(L∙h), (Yang et al. 2023). One of the interesting studies demonstrated that the use of inorganic nitrogen sources may influence the expression of L-LDH in the case of pure D-LA-producing Lactobacillus strains (Singhvi et al. 2017). Concerning the usage of other waste materials as substrate in one of the studies, L. rhamnosus was utilized to ferment cassava powder in a simultaneous saccharification and fermentation (SSF) mode, which produced 175 g/L LA with a yield of 0.71 g/g and productivity of 1.8 g/(L∙h) (Wang et al. 2010). Correspondingly, a multi-cycle repeated batch fermentation method was employed to convert fruit waste and cheese whey into LA by L. casei, yielding 397.1 g/L of LA in 12 days, with a productivity of 1.32 g/(L∙h) (Costa et al. 2024).

Metabolic engineering approaches for enhancing L-LA biosynthesis

Recent advancements in synthetic biology, particularly high-throughput gene editing, automated cloning platforms, and dynamic promoter circuits, have significantly enhanced microbial production phenotypes. Rather than bypassing traditional engineering frameworks, these modern toolsets enable highly precise, targeted metabolic regulation. This allows researchers to accurately balance cofactor availability, eliminate competing metabolic pathways, and deliberately tune enzyme expression to maximize lactic acid yield and volumetric productivity. These approaches principally involve redirecting metabolic flux to desired products through genetic modifications, empowering more efficient and high-yield production systems. LA fermentation can advance via homofermentative, heterofermentative, or Bifidum pathways. The homofermentative pathway—characterized by the presence of fructose-1,6-bisphosphate aldolase—translates up to 85% of glucose into LA with a yield of 2 ATP per glucose molecule. Conversely, obligate heterofermentative bacteria and Bifidobacterium lack aldolase. The heterofermentative mode classically results in about 50% conversion accompanied by downstream-complicating by-products. Notably, the Bifidum pathway (or bifid shunt) relies on fructose-6-phosphate phosphoketolase and represents the energetically most efficient mechanism for LA formation, generating 2.5 mol of ATP per mole of glucose consumed. Unlike the homolactic pathway which theoretically routes 100% of carbon to lactic acid (LA), the heterolactic mode imposes a severe carbon yield penalty, capping maximum theoretical conversion at roughly 50%. This efficiency loss is driven by the diversion of substrate carbon into volatile carbon dioxide (CO₂). Concurrently, liquid byproducts such as acetic acid and ethanol are accumulated in the broth. While CO₂ easily desorbs gaswise without hindering downstream operations, these soluble co-solvents significantly complicate downstream processing (DSP), demanding intensive fractional distillation or liquid–liquid extraction steps to meet polymer-grade LA purity standards.

In homolactic fermentation, glucose is chiefly processed through the Embden-Meyerhof-Parnas (EMP) pathway, which converts 1.0 mol of glucose into 2.0 mol of pyruvate, which are further reduced to 2.0 mol of LA, without generating CO₂. Homolactic pathways are categorized by their ease and high targetability, making them more amenable to genetic engineering to boost yields. Contrariwise, heterolactic fermentation comprises multiple enzyme co-metabolism steps, leading to by-product generation, which can hamper productivity and surge purification costs (Wang et al. 2021). Industrial production of LA depends entirely on homofermentative microbial strains, indeed, as their high concentration reduces these processing issues. To cope with these obstacles, synthetic biology methods aim to curtail by-product formation while sustaining cell growth, repeatedly by integrating LA production pathways into classical strains and renovating central metabolism. The metabolic pathway involved for LA production in various microbes is depicted in Fig.S1.

To overcome these metabolic diversions, recent genetic modifications have targeted specific operational bottlenecks rather than chasing absolute yield alone. When evaluating these engineered and evolved strains, comparing raw titers out of context can be misleading. For instance, several metabolic engineering efforts yield lower final LA concentrations compared to optimized wild-type bacterial setups (> 100 g/L). However, these engineered strains offer distinct, high-utility advantages designed to solve systemic biorefinery limitations. A primary industrial target is the elimination of the gypsum waste cycle through low-pH tolerance. By knocking out the native pyruvate decarboxylase (PDC1) gene and heterologously expressing a robust D-LDH pathway from Lactobacillus plantarum, researchers engineered the acid-tolerant yeast Pichia kudriavzevii (strain NG7) (Park et al. 2018). This engineered yeast achieves a high titer of (135 g/L) at a low pH of 3.6, operating efficiently under neutralizer-free conditions to eliminate downstream calcium sulfate waste. Similarly, to target the complex pentose sugar fractions found in second-generation biorefineries, S.cerevisiae was heavily modified through multi-copy LDH insertions paired with deletions of competing pathway genes (ERF2, GPD1, CYB2, PHO13, and ALD6) (Choi et al. 2024). This engineered yeast successfully ferments xylose feedstocks to accumulate 93 g/L of LA with a yield of 0.84 g/g allowing efficient valorization of lignocellulosic hydrolysates that conventional bacteria fail to process. Alternative strategies focus on maintaining bacterial efficiency while widening operational windows or reducing upstream processing costs. Through inter-generic protoplast fusion between L.delbrueckii and the acid-resistant Acetobacter pasteurianus, the bacterial hybrid strain FM1 was developed (Singhvi et al. 2015). Although it yields a modest concentration of approximately 45 g/L, it effectively drives bacterial fermentation down to a pH threshold of 4.0, minimizing base consumption. From an upstream cost-reduction perspective, adaptive laboratory evolution (ALE) has been utilized on filamentous fungi, such as Rhizopus oryzae (strain HZS6), to achieve direct fermentation of raw corncob xylose streams (Ma et al. 2016). This evolved strain yields 77.2 g/L of optically pure 100% L-LA without requiring expensive organic nitrogen supplements, demonstrating that lower-titer strains can provide superior economic profiles by bypassing capital-intensive biomass pretreatment and purification loops.

In relation to robust hosts like Saccharomyces cerevisiae, beyond the adaptive laboratory evolution (ALE) work, a study combined metabolic engineering and ALE to further augment L-LA synthesis. An adaptive evolution was employed to advance acid tolerance, resulting in an ultimate engineered S. cerevisiae strain generating 121.5 g/L of L-LA with a yield of 0.81 g/g in a 5.0-L fermenter. This work highlights how merging methods can impetus production limits. Additionally, leveraging cheaper substrates as a carbon source is another vital area of research. The bacterial strain, L. plantarum was engineered to ferment raw corn starch by deleting ldhD and larA-E genes, enabling it to generate 87 g/L of L-LA with an optical purity of 99.4% (Baek et al. 2016). A highly efficient strain has been established by breeding platform where heavy-ion mutagenesis with droplet enrichment techniques was combined together, in B. coagulans. The improved strain unveiled high osmotic tolerance and successfully produced 113.5 g/L of L-LA from sweet sorghum juice with the yield and productivity of 95% and 4.9 g/L/h, respectively (Yan et al. 2025). Metabolic engineering has been highly effective in optimizing L-LA production across numerous microbes for higher industrial feasibility. E. coli was altered by substituting its native D-LDH gene with an L-LDH from Streptococcus bovis strain, hindering the methylglyoxal pathway, and blocking the innate aerobic L-LDH gene. This engineered E. coli strain generated 50 g/L of L-LA with 99.9% optical purity and 93% yield from crude glycerol (Wu and Eiteman 2017). Lacticaseibacillus casei BL71 was engineered to produce 44.23 g/L of L-LA with a productivity of 0.8 g/(L∙h) using cheese whey as substrate (Catone et al. 2021). This exemplifies how engineering efforts are being engrossed on exploiting cost-effective substrates to advance sustainable and efficient L-LA production processes. The overall comparative studies on lactic acid production by wild and modified strains of various microbes have been discussed in Table S2.

Downstream processing (DSP) and advanced purification strategies

Downstream processing is a noteworthy part of the cost of the large-scale LA production process, which can comprise up to 50% of the total operating costs. The advancement of economically feasible and sustainable separation technologies is vital, and methods like integrated membrane separation appear to be promising, alongside precipitation, solvent extraction, membrane-based processes, electrodialysis, and ion exchange chromatography. The high cost of L-LA purification presents a major bottleneck in large-scale production. Therefore, the development of economically viable, environmentally sustainable separation technologies is significant.

Precipitation methods: operational baselines and sustainability bottlenecks

Precipitation remains the historical industrial benchmark for \(L\)-lactic acid (LA) recovery due to its operational simplicity and resilience to the unpredictable chemical matrices of crude fermentation broths. However, conventional calcium-based precipitation presents severe efficiency and environmental trade-offs. Utilizing calcium oxide (CaO) as a precipitant achieves a critically low standalone LA recovery rate of just 43% within 24 h, even when assisted by 25% (v/v) ethanol. While CaO marginally outperforms traditional calcium carbonate (CaCO₃) and calcium hydroxide (Ca(OH)₂) in neutralization kinetics, this poor mass yield renders standalone calcium precipitation economically unviable for modern, high-throughput biorefineries.

From a sustainability perspective, life-cycle assessments (LCAs) of calcium precipitation highlight severe environmental burdens. The mandatory addition of concentrated sulfuric acid to liberate the organic acid from the calcium lactate complex generates massive quantities of insoluble calcium sulfate (gypsum) waste approximately 1.0 to 1.5 tonnes of gypsum per tonne of purified LA. This creates severe solid-waste disposal challenges and yields heavily polluted, high-salinity wastewater streams that fail modern green chemistry standards and demand energy-intensive wastewater treatment loops.

To alleviate these economic and environmental bottlenecks, recent research focuses on alternative neutralizers:

Magnesium oxide (MgO) systems

Replacing calcium with MgO shifts the byproduct stream from low-value gypsum to magnesium lactate. This water-soluble intermediate can be direct-formulated into the food, animal feed, and pharmaceutical sectors (Wang et al. 2023). This approach eliminates the acidification-driven waste stream, drastically improving the process’s environmental footprint and overall cost-benefit index.

Advanced extraction and membrane separation: a comparative synthesis

To overcome the mass losses and high chemical consumption inherent to precipitation, advanced solvent extraction and membrane filtration networks are widely evaluated for their energy efficiency and continuous operation capacity.

Salting-out extraction (SOE)

Rather than relying on chemical precipitation, SOE systems utilize phase-separation dynamics to concentrate the product. Implementing an n-butanol and 60% (w/v) ammonium sulfate system at an optimized acidic pH of 2.5 successfully partitions LA into the top organic phase. This mechanism avoids clean-water dilution and eliminates gypsum formation entirely.

Synergistic organic solvents

Phase partition efficiency can be further driven by tuning solvent chemistry. Combining ethyl acetate with tributyl phosphate (TBP) as a synergistic organic phase at pH 2.5 and 25 °C achieves a high extraction efficiency of 85.95% (Kumar et al. 2020). While TBP enhances the distribution coefficient, its high raw material cost requires stringent solvent-recovery loops (via distillation) to maintain economic feasibility.

Nanofiltration (NF) fractionation flux bottlenecks

A major bottleneck in membrane separation is the trade-off between impurity rejection and product flux, which is heavily governed by the operating pH. For instance, a three-stage nanofiltration system utilizing an NF3 membrane on fermented straw biomass broth successfully retained 94% of unconverted sugars, protecting downstream units from carbohydrate fouling (Sikder et al. 2012). However, at an operating pH of 5.5, only 32% of the LA was allowed to permeate the membrane matrix. Because pH 5.5 sits well above the pKa of lactic acid (3.86), the acid exists primarily as dissociated lactate ions. These ions undergo strong electrostatic repulsion against the negatively charged membrane surface. This confirms that while the NF3 membrane is highly selective for sugar retention, operating under neutral-to-basic conditions introduces a severe mass-transfer limitation where 68% of the product is held back, requiring secondary filtration stages or pH adjustments to recover the target molecule.

Electrodialysis (ED) and bipolar membrane electrodialysis (BMED)

To bypass the flux limitations of traditional filtration, electromigration techniques like ED and BMED are deployed to simultaneously concentrate and convert LA salts without chemical addition. A two-stage ED system processing crude fermentation broth successfully achieved a high final LA titer of 151 g/L, driving sodium lactate conversion rates beyond 99% (Hb̌ová et al. 2004). This represents a highly efficient alternative to chemical acidification, as it eliminates the consumption of mineral acids and prevents subsequent salt waste generation.

Green emulsion liquid membranes (GELM)

Innovation in liquid membrane systems has evolved beyond single renewable solvent formulations (such as rice bran oil matrices). Current trends focus on highly tunable, sophisticated green solvent systems, including Natural Deep Eutectic Solvents (NaDESs) and tailored Ionic Liquids (ILs) (Schuh et al. 2023). These advanced GELM configurations offer highly selective solute transport and customizable affinity for LA, though their long-term emulsion stability and industrial scale-up costs remain under active evaluation.

Reactive distillation (RD)

For downstream schemes aiming for high chemical purity, reactive distillation offers simultaneous esterification, separation, and product removal within complex media. This integrated thermodynamic strategy improves overall selectivity and drastically reduces bulk solvent consumption. However, RD remains a highly energy-intensive strategy, and the presence of volatile fermentation impurities often creates operational hurdles, causing column fouling or side reactions that complicate thermal separation loops (Jianlong et al. 1994).

Integrated in situ and multi-stage processing

To completely circumvent the cumulative capital costs and product losses of step-by-step downstream purification, recent focus has shifted toward integrating recovery mechanisms directly within the upstream fermentation setup.

In situ extractive fermentation (adsorption and extraction)

Integrating separation methods directly within the bioreactor surmounts the severe product inhibition that typically stalls microbial growth and reduces inclusive process proficiency. Utilizing Amberlite IRA-67—a weak anion exchange resin—in a fed-batch extractive fermentation configuration with Bacillus strains successfully maintained free LA concentrations below cell-toxic thresholds, resulting in a 1.31-fold increase in LA productivity (Boonmee et al. 2016). Similar adsorbent integration strategies implemented for Lactobacillus casei fermentations yielded a 1.47-fold enhancement in productivity (Jianlong et al. 1994), proving that in situ product removal fundamentally amends microbial kinetics by controlling end-product toxicity.

Multi-stage hybrid cascades

When high-end polymer-grade purity ((> 99.5%)) is required for polylactic acid (PLA) synthesis, standalone methods are insufficient. Hybrid continuous cascades—such as an integrated ultrafiltration (UF) and NF network coupled directly with downstream ion exchange and vacuum evaporation—have successfully delivered LA purities exceeding 99.5% (Alexandri et al. 2018). This demonstrates that while individual steps like filtration or ion exchange suffer from unique bottlenecks (such as the 32% NF3 permeation or resin saturation), their strategic sequential integration yields an economically viable, sustainable, and high-purity industrial workflow. The comparative overview of costing, applicability, and life cycle assessment (LCA) impacts has been presented in Table S3.

PLA synthesis

Polylactic acid (PLA), a biodegradable thermoplastic, is synthesized mainly from LA via the polymerization method. Over 90% of commercially generated LA is derived from renewable starchy substrates like corn, rice, wheat, and cassava, which undergo enzymatic hydrolysis to generate glucose molecules. This glucose is then fermented by lactic acid bacteria (LAB) to yield LA. Following downstream purification, the transformation of L-LA into polylactic acid (PLA) shifts entirely from a biological process to a distinct, abiotic chemical synthesis. PLA polymerization proceeds strictly via chemical pathways utilizing the bifunctional nature of the purified LA monomer, which contains both an active hydroxyl (-OH) and a carboxyl (-COOH) group (Othman et al. 2017). Because these functional groups are capable of reacting intermolecularly, they drive chain-growth propagation to form high-molecular-weight polymers independent of the upstream microbial system. Although polymerization is a challenging process due to its multifaceted chemical mechanisms and the need for precise control of stereochemistry. Current discoveries in asymmetric organic catalysis, (by Benjamin List and David MacMillan) designate potential for more competent chemical synthesis of chiral LA isomers in the future (Yu et al. 2023).

LA monomers occur in two optical isomers, D-LA and L-LA, which give rise to four lactide stereoisomers i.e., L-lactide, D-lactide, meso-lactide, and DL-lactide. Therefore, PLA synthesis can lead to four conformations: poly(L-lactide) (PLLA), poly(D-lactide) (PDLA), poly(meso-lactide), and poly(rac-lactide) (PDLLA). Among these, PLLA shows better thermal and mechanical properties. The stereochemical configuration and optical purity of the constituent monomers directly dictate the crystallization kinetics, thermal properties, and mechanical performance of high-molecular-weight PLA. While pure poly(L-lactide) (PLLA) forms a highly semi-crystalline, rigid, and brittle material, the controlled incorporation of small fractions (typically 1–10%) of the D-LA enantiomer into the polymer chain introduces structural irregularities that disrupt tight molecular packing. This stereorandomization lowers both the crystal growth rate and the final degree of crystallinity, effectively increasing the mobility of the amorphous phases to yield a more ductile and flexible polymer matrix. Conversely, blending equal ratios of pure PLLA and pure PDLA triggers stereocomplexation, where interlocking enantiomeric chains form highly ordered crystals that dramatically increase thermal stability and mechanical strength rather than flexibility, confirming that the precise chiral assembly of PLA chains commands their final macroscopic material properties (Zhao et al. 2023).Generally, polymerization of PLA occurs via: (a) direct condensation polymerization, (b) azeotropic dehydration, (c) ring-opening polymerization (ROP), and (d) enzymatic polymerization as presented in Fig. 4. These methods have distinct problems and advantages as well which influence the eventual properties of PLA. Hence, it is necessary to select proper polymerization methods to attain the anticipated characteristics of PLA to be used for explicit applications.

Fig. 4.

Pathway involved in the synthesis of PLA using lactic acid as precursor derived from lignocellulosic waste

Direct condensation polymerization (DCP)

DCP method involves the synthesis of PLA via condensation of hydroxyl (–OH) and carboxyl (–COOH) functional groups in LA molecules. This method contains several techniques, including melt condensation polymerization (MCP), melt-solid polycondensation (MSP), and solution polymerization (Hu et al. 2016).

MCP is a method where PLA is synthesized from LA by means of catalysts, such as SnCl₂/p-toluenesulfonic acid, under condensed pressure and temperatures at around 180–230 °C. Current developments like twin-screw extrusion have empowered continuous polymerization, aiding in accomplishing higher molecular weights (up to 150,000) which can improve PLA properties (Yu et al. 2023).

MCP approach syndicates a melt-phase oligomerization phase, which generates low-molecular-weight PLA (~ 5000–20,000), with succeeding solid-state reactions performed between the glass transition and melting temperatures. The dynamic crystallization technique with talc nucleators showed the boost in efficiency by 30%, resulting in higher molecular weights (> 200,000) (Aliev et al. 2024).

SP method for PLA synthesis uses solvents like xylene to remove water and lower down the viscosity of the solution. Although promising research demonstrates it can considerably advance PLA properties—for example, chitosan-modified graphene oxide (GO) amended oxygen barrier by 55 times, and PDMS-PEG elastomers tripled elongation—the method faces major issues. Main problems include high cost of solvent recovery (30–40% of total expenses) and hitches in exactly governing molecular weight with polymerization. The required use of solvents also surges production costs and creates an environmental pollution risk (Rezvani Ghomi et al. 2021).

Regardless of its ease and low cost, a foremost restraint of DCP method is its innate failure to produce high-molecular-weight (HMW) PLA. The reaction between LA molecules is a reversible equilibrium, and the water, a byproduct formed during polymerization, dynamically hinders the onward reaction. Therefore, this method is basically restricted to synthesizing low-molecular-weight (LMW) PLA. The serious aspect for increasing MW is the effective elimination of this produced water; factually, this difficulty has pointedly constrained the wide applicability of this method.

Azeotropic dehydration condensation (ADC)

A main limitation of the DCP method is the trouble in efficiently removing the water produced through the reaction. The generated water alters the reaction equilibrium toward the reactants, which avoids the formation of high-molecular-weight PLA. Besides water removal problem, numerous other aspects impact both the polymerization rate and the final molecular weight of the polymer. These factors include the catalyst type, choice of solvent, temperature, and the existence of impurities.

Impurity in the reaction mixture has a substantial effect on the final molecular weight of PLA as a result of the “end-capping phenomenon.” During end-capping, impurities can cap the reactive chain ends of the growing polymer, efficiently stumbling further polymerization which averts the formation of longer polymer chains (Ramezani Dana and Ebrahimi 2023). Residual monomers or catalyst residues can lead to the depolymerization of PLLA during melt processing, causing a loss in molecular weight. Water removal is critical, as verified by methods that employ a dehydrating agent for water removal in a closed environment, permitting for very high molecular weights to be attained without organic solvents.

Ring-opening polymerization (ROP) of lactide

ROP of lactide is a broadly used effectual method for industrial PLA production, yielding high-molecular-weight polymers with controllable properties. This method comprises using lactide which can be exactly measured by regulating factors like temperature, catalyst concentration and time to accomplish particular properties such as high stereo purity (> 99.5%) and tunable crystallinity (30–60%) for medical-grade PLA (Song et al. 2022). Various catalytic schemes offer diverse performance trade-offs; for example, while stannous octoate ((Sn(Oct)₂₎ is widely used and FDA-approved for food contact, organocatalysts like TBD·HCl offer superior control with minimal racemization (< 50 ppm) but are water-sensitive (Theodorou et al. 2023)Al/Nd bimetallic systems, which facilitate stereoselective chain growth to produce high-performance PLA (Mw > 250 kDa, PDI < 1.6) (Viamonte-Aristizábal et al. 2021) For large-scale manufacturing, processes utilizing co-catalysts and reactive extrusion can attain very high molecular weights (Mw > 350 kDa) and high conversions (98%), ensuing in enhanced mechanical properties (Li et al. 2021).

Enzymatic polycondensation (EPC)

While abiotic chemical routes dominate commercial manufacturing, biological synthesis strategies offer a sustainable, single-pot alternative for producing PLA under ambient conditions. From a biochemical perspective, native “lactic acid polymerases” do not exist. Instead, direct microbial PLA synthesis is achieved by repurposing and metabolically engineering polyhydroxyalkanoate (PHA) synthases (PhaC) predominantly Class I from Ralstonia eutropha and Class II from Pseudomonas species (Balla et al. 2021). Because wild-type PhaC enzymes exclusively polymerize hydrophobic hydroxyacyl-CoAs, synthesis of the hydrophilic PLA backbone requires a multi-enzyme cascade. First, an engineered propionyl-CoA transferase (Pct) from Clostridium propionicum converts free intracellular L- LA into the active thioester intermediate, lactyl-CoA. Subsequently, a molecularly evolved PhaC variant accepts lactyl-CoA as a substrate to catalyze chain-propagation, allowing for direct in vivo intracellular PLA accumulation within engineered bacterial cell factories (Balla et al. 2021). A major bottleneck of this microbial pathway remains its low catalytic efficiency. Wild-type PHA synthases possess high substrate affinity (Km) for native targets like 3-hydroxybutyryl-CoA but exhibit severe steric hindrance and poor turnover rates (K_cat) when encountering lactyl-CoA. This catalytic mismatch leads to low polymer accumulation rates and premature chain termination, often limiting the production to low-molecular-weight oligomers. To circumvent these limitations, direct metabolic engineering has focused on optimizing substrate flux and structural enzyme modifications. For example, Tan et al. (2022) engineered a photosynthetic cyanobacterial strain by co-expressing a tailored metabolic pathway with an immobilized, evolved PhaC synthase (Tan et al. 2022). By optimizing carbon flux directly from photosynthetic fixation, this system converted dioxide (CO₂) directly into high-molecular-weight PLA (> 50 kg mol⁻¹)), demonstrating a notable 270-fold upsurge in productivity compared to early-generation base strains (Tan et al. 2022). Complementing in vivo cell factories, in vitro enzymatic polycondensation (EPC) utilizing extracellular hydrolases offers precise stereoregulatory control without cell maintenance costs. While traditional EPC processes struggle with low reaction kinetics and thermodynamic equilibrium limitations in aqueous media, non-aqueous systems utilizing green solvents have fundamentally improved efficiency. A chemically modified Candida antarctica lipase B (CALB) optimized via surface charge engineering achieved a near-complete 99% depolymerization and subsequent repolymerization of PLA when paired with customized ionic liquids (ILs) at 90 °C (Xue et al. 2022). This approach bypasses volatile organic solvents and supports a closed-loop chemical recycling model (Xue et al. 2022). The primary advantage of the EPC and in-cell PHA-synthase pathways over traditional chemical ring-opening polymerization (ROP) is the capability to operate under mild, ambient conditions without generating hazardous heavy-metal residue (e.g., stannous octoate) or unreacted volatile monomers. However, future directions in biological PLA synthesis must prioritize structural tunnel engineering of the PhaC substrate-binding pocket to minimize lactyl-CoA steric clashing, alongside the development of high-affinity Pct variants to mitigate the cellular toxicity induced by accumulated intracellular acyl-CoA pools.

Applications of PLA

Following decades of development, the industrial production technology for PLA has ripened substantially. Attributing to its exceptional properties, PLA is now a multipurpose bioplastic used across many areas, including agriculture, textiles, biomedical, packaging, transportation, and 3D/4D printing. The details about the various applications of PLA in different fields have been discussed in Supplementary Section S1.

Challenges, industrial prospects, and future frameworks

The global transition toward high-purity (L)-lactic acid (LA) as a green platform chemical requires resolving interconnected bottlenecks across substrate sourcing, host engineering, and bioprocess control. Developing an economically viable process requires optimizing volumetric productivity and optical purity without increasing the downstream waste footprint.

Transitioning to industrial side-streams and multi-substrate pretreatment

While first-generation (1G) food crops offer high yields, their use creates severe ethical competition with food security. Conversely, second-generation (2G) lignocellulosic biomass (LCB) avoids this conflict but requires energy-intensive chemical or enzymatic pretreatments that generate toxic degradation byproducts (such as furfural and 5-hydroxymethylfurfural) which inhibit microbial growth.

To overcome these economic and chemical limitations, future industrial frameworks must prioritize low-cost agro-industrial side-streams and municipal solid waste residues. Co-utilizing heterogeneous waste matrices such as crude industrial glycerol, sugarcane bagasse, sugarcane molasses, and dairy whey permeates presents an excellent strategy for reducing raw material costs. However, these complex side-streams introduce distinct processing challenges:

Nutritional imbalances

They often feature highly skewed carbon-to-nitrogen (C:N) ratios that can disrupt steady-state cell maintenance.

Batch-to-batch volatility

Variabilities in salt concentrations and heavy metal impurities can destabilize continuous, long-term fermentation operations.

Resolving physiological bottlenecks in microbial production hosts

Sustaining high-titer production requires resolving the inherent metabolic constraints of traditional and non-conventional production hosts:

Lactic acid bacteria (LAB)

While LAB strains excel at homofermentative yields, they are highly sensitive to product inhibition. As free lactic acid accumulates, it acidifies the extracellular medium and passes back through the cell membrane, which lowers the inner cytosolic pH and deactivates essential glycolytic enzymes.

Fungal and yeast systems

Utilizing acid-tolerant yeasts or molds can bypass the need for expensive neutralizing agents. However, these organisms often possess competing pathways that divert pyruvate into ethanol or acetate byproducts, requiring targeted knockouts of native pyruvate decarboxylase (PDC) networks.

Algal and photosynthetic strains

Photosynthetic strains offer a direct pathway for capturing carbon dioxide (\(\text{CO}_{2}\)), but their space–time yields remain heavily constrained by the low carboxylation efficiency and poor kinetics of the native Ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco) enzyme under high oxygen concentrations. Bypassing these host limitations requires combining directed evolution of the host’s enzymes with metabolic engineering techniques like CRISPR-driven gene multiplexing and targeted gene ion mutagenesis (Baek et al. 2016).

Machine learning (ML) and AI-driven process optimization

Because biological fermentations are highly non-linear, dynamic systems, deploying artificial intelligence (AI) and machine learning (ML) models is crucial for predicting and managing complex bioprocess parameters. In Yarrowia lipolytica fermentations, the application of predictive ML models solved a major metabolic bottleneck (Vinestock et al. 2024). Y. lipolytica is highly sensitive to the interaction between complex carbon feeding rates and dissolved oxygen (DO) levels; under suboptimal configurations, the cell defaults to accumulating citric acid, which severely reduces LA yields. The implemented ML model successfully predicted the non-linear interaction between these variables in real time. This enabled the system to maintain optimal substrate feeding intervals that suppressed the byproduct loop, ensuring high-yield flux toward the target \(L\)-LA pathway.

Similarly, advanced ensembled frameworks like PERISCOPE-Opt utilize support vector machines (SVM) and random forest (RF) algorithms to map multi-variable inputs (such as pH, temperature, and trace mineral fluctuations) against cell expression profiles (Packiam et al. 2022). These AI-driven approaches minimize the need for slow, resource-intensive trial-and-error experiments, allowing industrial biorefineries to maintain high structural productivity even when utilizing volatile, low-cost waste streams.

Conclusions

LA production from renewable substrates in a cost-effective, efficient, and environmentally sustainable manner still remains a major challenge. In this review article, state-of-the-art advances in biological L-LA production, covering feedstocks, microbial strains, fermentation processes, and separation technologies, have been delineated. Main problems comprise substrate–food struggle, pretreatment intricacy, costly production process, and low recovery rates during separation of LA from broth. Forthcoming efforts should focus on the investigation of cheaper renewable substrates, new microbial resources, higher metabolic performance, and better separation approaches. Lowering energy consumption and augmenting process efficacy will be critical. Sustained modernization in renewable substrate utilization is crucial for accomplishing economically and environmentally viable production of LA. Polylactic acid (PLA) is a foremost bio-based polymer employed in various fields including biomedical, packaging, and textile industries, presently contributing 31% of the PLA market. PLA production is chiefly attained via ring-opening polymerization (ROP) for greater efficiency, yet its low-molecular-weight in direct polycondensation (DPC) and the enzymatic polymerization demonstrate restrictions. Performance improvement arises from modifications in crystallinity via suitable nucleating agents, stereocomplex crystal formation, and augmented processing, while innovative processing technologies like 3D/4D printing enable specialized applications. Though its slow ambient degradation is still a concern. Upcoming developments will emphasize on novel synthetic approaches, nanocomposites functionalization and controlled degradation mechanisms, positioning PLA as a keystone of sustainable industrial evolutions amid universal regulations.

Supplementary information

Below is the link to the electronic supplementary material.

Author contributions

Conceptualization, M.S; methodology, M.S; software, M.S..; validation, M.S.;formal analysis, M.S.; investigation, M.S.; resources, M.S.; data curation, M.S.; writing—original draft preparation, M.S.; writing—review and editing, M.S. and T.Z.; visualization, M.S.; supervision, M.S.; project administration, M.S.; funding acquisition, M.S., T.Z., and S.S. All authors have read and agreed to the published version of the manuscript.

Funding

The work was supported by grants from Ramalingaswami Re-entry Fellowship (BT/RLF/Re-entry/27/2021), Department of Biotechnology (DBT), Government of India and the Japan Society for the Promotion of Science (JSPS) fellowship (JSPS/IP/25001).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Competing interests

The authors declare no competing interests.