Table 1.
Progresses of β-carotene biosynthesis in the last decade
| Strain | Strategy | Yield | Year | Refs. |
|---|---|---|---|---|
| Native producers | ||||
| Blakeslea trispora | Development of new cultivation equipment | 44.56 mg/g DCW, 8 days (bubble column reactor) | 2012 | Nanou et al. (2012) |
| Blakeslea trispora | Increase of oxygen concentration and induced high oxidative stress via addition of 3% (v/v) liquid paraffin |
715 mg/L 84 h (shake flask) |
2013 | Hu et al. (2013) |
| Mucor circinelloides | Strain mutagenesis with UV and NTG | 4 mg/g DCW (shake flask) | 2016 | Zhang et al. (2016b) |
| Blakeslea trispora | Addition of sodium acetate (NaAC) in mated B. trispora |
59.91 mg/g DCW 2130 mg/L, 8 days (shake flask) |
2016 | Jing et al. (2016) |
| Blakeslea trispora | Optimization of cultivation by single factor and response surface test | 523.8 mg/L (shake flask) | 2020 | Chang-he et al. (2020) |
| Blakeslea trispora | Protoplast fusion between ATCC 14,272( +) and ATCC 14,272(−) | 36.93 mg/gDW (shake flask) | 2021 | Wang et al. (2021b) |
| Blakeslea trispora | Regulation of light and active oxygen | 5.0 mg·g DW (shake flask) | 2021 | Luo et al. (2021) |
| Rhodotorula glutinis | Optimization of carbon:nitrogen (C/N) ratios (20:1, 50:1, 70:1, and 100:1) to analyze carotenoid and lipid biosynthesis | N.A | 2017 | Tkáčová et al. (2017) |
| Rhodotorula glutinis | Supplementation of vegetable oils as carbon source and optimization of bioreactor |
0.36 mg/L 156 h (agitator bioreactor) |
2019 | Yen et al. (2019) |
| Heterologous hosts | ||||
| S. cerevisiae | Overexpressing HMG-CoA reductase gene and adding ergosterol synthesis inhibitor ketoconazole | 6.29 mg/g DCW | 2012 | Yan et al. (2012) |
| S. cerevisiae | Deletion of gene rox1, yjl064w and ypl062w | ~ 2.1 mg/g DCW | 2013 | Ozaydin et al. (2013) |
| S. cerevisiae | Design of a set of marker recyclable integrative plasmids (pMRI) for decentralized assembly of reconstructing controllable multi-gene pathways by employing the GAL regulatory system |
7.41 mg/g DCW (shake flask culture) |
2013 | Xie et al. (2014) |
| S. cerevisiae | Introduction of crtE, crtYB and crtI from Phaffia rhodozyma into S. cerevisiae INVSc1; Additional expression of the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase (cHMG1) |
528.8 ± 13.3 μg/g DCW (shake flask culture) |
2014 | Shi et al. (2014) |
| S. cerevisiae | Increasing the gene transcription of MVA pathway, by reducing temperature from 30℃ to 4℃;supplementation of 30 mg/L triclosan, an inhibitor of fatty acid synthesis |
4.94 mg/g DCW (shake flask culture) |
2015 | Sun et al. (2015) |
| S. cerevisiae | Enriching unsaturated fatty acids (UFAs) contents by exogenous supplementation or strengthening their biosynthesis | 2.83 mg/g DCW | 2016 | Sun et al. (2016) |
| S. cerevisiae | Discovery the relationship between carotenoid biosynthesis and cell membrane (CM) fluidity via genome-wide transcriptional analysis as well as optimization of CM fluidity by supplying linoleic acid |
4.65 mg/g DCW (shake flask culture) |
2016 | Liu et al. (2016a) |
| S. cerevisiae | Development of an inducer/repressor-free sequential control strategy regulated by glucose concentration for two-phase cultivation of engineering strains |
20.79 mg/g DCW (fed-batch fermentation) |
2016 | Xie et al. (2015a) |
| S. cerevisiae | Identification and overexpression of novel gene targets outside the isoprenoid pathway, including genes encoding 14–3-3 protein (Bmh1), class E protein of the vacuolar protein-sorting pathway (Did2), translation initiation factor (Tif5), and vacuolar H( +)-ATPase subunit 1 (Voa1) | 5.9 ± 0.1 mg/g DCW | 2017 | Li et al. (2017) |
| S. cerevisiae | Introduction of a beta-carotene biosynthetic pathway containing crtYB, crtI, and crtE from Xanthophyllomyces dendrorhous in a xylose-fermenting S. cerevisiae | 772.8 mg/L | 2020 | Sun et al. (2020) |
| S. cerevisiae | Expression of lipases of LIP2, LIP7, LIP8, and introduction of beta-carotene biosynthetic pathway from Xanthophyllomyces dendrorhous | 46.5 mg/g DCW | 2021 | Fathi et al. (2021) |
| E. coli | Engineering MEP module and β-carotene synthesis module; engineering of ATP synthesis, pentose phosphate pathway (PPP) and TCA modules; |
2.1 g/L 60 mg/g DCW (fed-batch fermentation) |
2013 | Zhao et al. (2013) |
| E. coli | Overexpression of the complete β-carotene synthetic pathway (including dxs, ipiHP1, crtE, crtB, crtI, and crtY genes) and the entire MVA pathway (namely, mvaE, mvaS, mvaK1, mvaK2, mvaD, and idi genes), |
2.47 g/L 72 mg/g DCW (fed-batch culture) |
2013 | Nam et al. (2013) |
| E. coli | Improving the supply of precursor-IPP and GPP by optimization of MEP pathway and introduction of hybrid MVA pathway | 256.8 mg/L in flask culture and 3.2 g/L in fed-batch fermentation | 2014 | Yang and Guo (2014) |
| E. coli | Engineering the cell membrane in both morphological and biosynthetic aspects by overexpressing membrane-bending proteins and engineering the membrane synthesis pathway | 44.2 mg/g DCW (shake flask culture) | 2017 | Wu et al. (2017) |
| E. coli | Knockout of a few proteins related to the formation mechanism of outer membrane vesicles like tolR and nlpI were to promote the excretion of β-carotene; overexpression of both AccABCD and PlsBC to supplement the loss of membrane components | 44.8 mg/g DCW (shake flask cultivation) | 2019 | Wu et al. (2019a) |
| E. coli | Regulation of central carbon metabolism by knockout of zwf and pts genes and improving NADPH supply by overexpression of nadk gene | 266.4 mg/L in flask culture and 2579.1 mg/L in bioreactor fermentation | 2020 | Wu et al. (2020b) |
| E. coli | Integration of systems metabolic engineering, cell morphology engineering, inner- and outer-membrane vesicle formation, and cultivation optimization | 343 mg/L | 2021 | Yang et al. (2021) |
| Yarrowia lipolytica | Optimization of promoter strength and gene copy number |
4 g/L (fed-batch fermentation) |
2017 | Gao et al.( 2017) |
| Yarrowia lipolytica | Development of a combinatorial synthetic biology approach based on Golden Gate DNA assembly to screen the optimum promoter–gene pairs for each transcriptional step |
6.5 g/L 90 mg/g DCW (fed-batch fermentation) |
2018 | Larroude et al. (2018) |
| Yarrowia lipolytica | Promoting the synthesis of precursor substrates by overexpression of hexokinase (Hxk) and hydroxymethylglutaryl-CoA synthase (Erg13) | 2.4 g/L (fed-batch fermentation) | 2020 | Qiang et al. (2020) |
| Yarrowia lipolytica | Construction of codon-adapted CarRA and CarRB and maintaining metabolic balance by regulation of the expression level of enzymes involved in rate-limiting steps | 1.7 g/L and 21.6 mg/g DCW (fed-batch fermentation) | 2021 | Liu et al. (2021b) |