Table 1.
Production of isoprenoids by engineered microorganisms.
| Isoprenoids produced | Host | Approach | Culture conditions | Yield/Titer | References |
|---|---|---|---|---|---|
| Lycopene | E. coli | Systematic (model-based) methods; Combinatorial (transposition-based) methods; Gene knockout. | Shake-flask fermentation | 18 mg/g DCW | [11] |
| Lycopene | E. coli | Central metabolic genes knockout; Amplification of MEP pathway genes | Shake-flask fermentation | 7.55 mg/g DCW | [12] |
| Lycopene | E. coli | Overexpression of native dxs; Other optimization methods (promoters, vectors, strains) | Shake-flask fermentation | 16.8 mg/L | [13] |
| Lycopene | E. coli | Introduction of a heterologous MVA pathway; Overexpressing Bacillus licheniformis idi | Shake-flask fermentation | 198 mg/g DCW | [15] |
| Lycopene | E. coli | Optimization of MVA pathway; Promoter engineering | Fed-batch fermentation | 20.25 mg/g DCW | [16] |
| Lycopene | E. coli | Increase ATP and NADPH; Engineering TCA modules; Overexpression of dxs∖idi∖crtE | Fed-batch fermentation | 50.602 mg/g DCW | [17] |
| Lycopene | E. coli | Application of the targeted engineering strategy | Fed-batch fermentation | 34.3 mg/g DCW | [18] |
| Lycopene | E. coli | Co-expression of the DXP and MVA pathway | Fed-batch fermentation | 32 mg/g DCW | [19] |
| Lycopene | E. coli | Application of CIChE | Shake-flask fermentation | 33.43 mg/g DCW | [21] |
| Lycopene | E. coli | Optimization of the lycopene biosynthetic genes; Overexpressing the MEP pathway (dxs-idi-ispDF) | Shake-flask fermentation | 448 mg/g DCW | [22] |
| Lycopene | S. cerevisiae | Combination of directed evolution and metabolic engineering strategy | Fed-batch fermentation | 24.41 mg/g DCW | [23] |
| Lycopene | S. cerevisiae | Combination of host engineering and pathway engineering | Fed-batch fermentation | 55.56 mg/g DCW | [25] |
| Lycopene | Y. lipolytica | Deletion of POX1 and GUT2 | Shake-flask fermentation | 16 mg/g DCW | [26] |
| Lycopene | S. avermitilis | Activation of the silent lycopene synthetic gene cluster | Shake-flask fermentation | 82 mg/g DCW | [27] |
| β-cartoene | E. coli | Plasmid-expressing the lower MVA pathway and idi from S. cerevisiae, Plasmid-expressing the upper MVA pathway from Enterococcus faecalis, Bacillus subtilis dxs and fni, and GPPS2 from Abies grandis; Plasmid-expressing the β-cartoene synthetic pathway. | Fed-batch fermentation | 60 mg/g DCW | [28] |
| β-cartoene | E. coli | Combined engineering of the MEP, the β-carotene synthetic, the TCA and the pentose phosphate (PP) modules by artificial modulation parts | Fed-batch fermentation | 3.2 g/L | [29] |
| β-cartoene | E. coli | Optimizing the biosynthetic pathway | Fed-batch fermentation | 2.0 g/L | [30] |
| β-cartoene | S. cerevisiae | Decentralized assemble strategy | Shake-flask fermentation | 7.41 mg/g DCW | [31] |
| β-cartoene | S. cerevisiae | Using the inducer/inhibiter-free sequential control strategy to sequentially control the expression of the carotenoid pathway, the MVA pathway and the competitive squalene pathway by glucose in the culture broth, | Fed-batch fermentation | 20.79 mg/g DCW, 1156 mg/L | [32] |
| Zeaxanthin | E. coli | Optimization of the zeaxanthin biosynthetic pathway | Shake-flask fermentation | 11.95 mg/g DCW | [38] |
| Zeaxanthin | E. coli | Introduction of a dynamically controlled TIGR-mediated MVA pathway | Fed-batch fermentation | 23.16 mg/g DCW | [39] |
| Astaxanthin | E. coli | Chromosomal expressing the optimized synthetic pathway | Shake-flask fermentation | 7.50 mg/g DCW | [41] |
| Astaxanthin | E. coli | RBS-modulated expression of the astaxanthin biosynthetic genes | Shake-flask fermentation | 5.8 mg/g DCW | [42] |
| Astaxanthin | E. coli | Plasmid-overexpression of Pantoea ananatis crtEIB, Pantoea agglomerans crtYZ, Brevundimonas sp. SD212 crtW and E. coli idi | 8.64 mg/g DCW | [43] | |
| Astaxanthin | S. cerevisiae | Introduction of codon-optimized Haematococcuspluvialis crtZ and bkt | Shake-flask fermentation | 4.7 mg/g DCW | [44] |
| Astaxanthin | S. cerevisiae | combinatorial metabolic engineering and protein engineering | Shake-flask fermentation | 8.10 mg/g DCW | [45] |
| Astaxanthin | C. glutamicum | Balanced expression of crtW and crtZ | Shake-flask fermentation | 0.4 mg/L/h | [46] |
| Isoprene | E. coli | Introduction of MVA pathway, codon and RBS optimization, deleted nine relevant genes to express ispS | Shake-flask fermentation | 1832 mg/L | [48] |
| Isoprene | E. coli | Chromosomal expressing the MVA lower pathway; Plasmid-expression of the MVA upper pathway; Plasmid-expression of mvk from Methanosarcina mazei and isoprene synthase gene from Populus alba | 14 L fed-batch fermentation | 60 g/L | [49] |
| Isoprene | E. coli | Overexpression of MEP and MVA pathway; Plasmid-expressing mvk from Methanosarcina mazei and isoprene synthase gene from Populus alba | Fed-batch fermentation | 24 g/L | [50] |
| Isoprene | S. cerevisiae | Dual metabolic engineering of cytoplasmic and mitochondrial acetyl-CoA utilization | Fed-batch fermentation | 2527 mg/L | [51] |
| Isoprene | S. cerevisiae | Combining the two-level expression system and directed evolution of ISPS | Fed-batch fermentation | 3.7 g/L | [52] |
| Isopentenol | E. coli | Introduction of MVA pathway; Expressing BsNudF gene | Shake-flask fermentation | 1.3 g/L | [54] |
| Isopentenol | E. coli | Constructing the MVA IPP-bypass pathway | Shake-flask fermentation | 705 mg/L | [56] |
| Isopentenol | E. coli | RBS engineering of nudB; Expressing the Idi-NudB fusion protein | Shake-flask fermentation | 2.23 g/L | [57] |
| Myrcene | E. coli | Co-overexpression of MVA pathway, AgGPPS and ms from Quercus ilex L. | Shake-flask fermentation | 58.19 mg/L | [58] |
| Myrcene | E. coli | Introducing the MVA lower pathway; Expressing the MVA upper pathway in combination with AgGPPS and SabS1 | Fed-batch fermentation | 2.65 g/L | [59] |
| Pinene | E. coli | Introduction of MVA pathway; Expressing AgGPPS-Pt30 fusion protein | Fed-batch fermentation | 0.97 g/L | [60] |
| Pinene | E. coli | Introduction of MVA pathway; Expressing AgPS-AgGPPS fusion protein | Shake-flask fermentation | 32.4 mg/L | [61] |
| Pinene | E. coli | Introduction of MVA pathway; Expressing PSmut-AgGPPS fusion protein | Shake-flask fermentation | 150 mg/L | [62] |
| Limonene | E. coli | Introduction of MVA pathway, Expressing the AgGPPS–LS fusion protein | Shake-flask fermentation | 435 mg/L | [63] |
| Farnesene | E. coli | Introduction of MVA pathway; Expressing the codon-optimized FS-IspA fusion protein | Shake-flask fermentation | 380 mg/L | [67] |
| Farnesene | E. coli | Application of In vitro reconstitution and targeted proteomics; Overexpression of Idi with IspA and AFS in E. coli expressing synthetic MVA pathway | Shake-flask fermentation | 1.1 g/L | [68] |
| Farnesene | S. cerevisiae | Introduction of the artificial acetyl coenzyme biosynthetic pathway (contained Dickeya zeae aldehyde dehydrogenase (acylating), Leuconostoc mesenteroides xylulose-5-phosphate specific phosphoketolase and Clostridium kluyveri phosphotransacetylase) with the NADH-consuming HMG-CoA reductase from Silicibacter pomeroyi | 200,000 L bioreactor fed-batch fermentation | 130 g/L | [69] |
| Bisabolene | E. coli | Co-expressing the codon-optimized AgBIS and the optimized MVA pathway | Shake-flask fermentation | 912 mg/L | [70] |
| Bisabolene | S. cerevisiae | Co-expressing the codon-optimized AgBIS and the optimized MVA pathway | Shake-flask fermentation | 994 mg/L | [70] |
| Bisabolene | S. cerevisiae | Screening the yeast knockout libraries; Co-expressing the MVA pathway and BIS gene | Fed-batch fermentation | 5.2 g/L | [72] |
| Farnesol | E. coli | Co-expressing ispA and the MVA pathway | Shake-flask fermentation | 135.5 mg/L | [73] |
| Farnesol | E. coli | Overexpressing ispA, pgpB and the MVA pathway | Shake-flask fermentation | 526.1 mg/L | [74] |
| Farnesol | S. cerevisiae | Overexpressing the truncated HMG-CoA reductase | 5L fed-batch fermentation | 145 mg/L | [75] |