Chandran SS, Kealey JT, Reeves CD. Microbial production of isoprenoids. Process Biochem. 2011;46(9):1703–10. https://doi.org/10.1016/j.procbio.2011.05.012.
Google Scholar
Moser S, Pichler H. Identifying and engineering the ideal microbial terpenoid production host. Appl Microbiol Biotechnol. 2019;103(14):5501–16. https://doi.org/10.1007/s00253-019-09892-y.
Google Scholar
Masyita A, Sari RM, Astuti AD, Yasir B, Rumata NR, Emran TB, et al. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chem: X. 2022;30(13):100217. https://doi.org/10.1016/j.fochx.2022.100217.
Google Scholar
Vickers CE, Williams TC, Peng B, Cherry J. Recent advances in synthetic biology for engineering isoprenoid production in yeast. Curr Opin Chem Biol. 2017;40:47–56. https://doi.org/10.1016/j.cbpa.2017.05.017.
Google Scholar
Shang J, Feng D, Liu H, Niu L, Li R, Li Y, et al. Evolution of the biosynthetic pathways of terpene scent compounds in roses. Curr Biol. 2024;34(15):3550–63. https://doi.org/10.1016/j.cub.2024.06.075.
Google Scholar
Bell EL, Finnigan W, France SP, Green AP, Hayes MA, Hepworth LJ, et al. Biocatalysis. Nat Rev Methods Primers. 2021;1(1):46. https://doi.org/10.1038/s43586-021-00044-z.
Google Scholar
Schneider A, Lystbaek TB, Markthaler D, Hansen N, Hauer B. Biocatalytic stereocontrolled head-to-tail cyclizations of unbiased terpenes as a tool in chemoenzymatic synthesis. Nat Commun. 2024;15(1):4925. https://doi.org/10.1038/s41467-024-48993-9.
Google Scholar
Chen X, Zhang C, Lindley ND. Metabolic engineering strategies for sustainable terpenoid flavor and fragrance synthesis. J Agric Food Chem. 2020;68(38):10252–64. https://doi.org/10.1021/acs.jafc.9b06203.
Google Scholar
Schempp FM, Drummond L, Buchhaupt M, Schrader J. Microbial cell factories for the production of terpenoid flavor and fragrance compounds. J Agric Food Chem. 2018;66(10):2247–58. https://doi.org/10.1021/acs.jafc.7b00473.
Google Scholar
Meadows AL, Hawkins KM, Tsegaye Y, Antipov E, Kim Y, Raetz L, et al. Rewriting yeast central carbon metabolism for industrial isoprenoid production. Nature. 2016;537(7622):694–7. https://doi.org/10.1038/nature19769.
Google Scholar
Wu W, Maravelias CT. Synthesis and techno-economic assessment of microbial-based processes for terpenes production. Biotechnol Biofuels. 2018;11:294. https://doi.org/10.1186/s13068-018-1285-7.
Google Scholar
Sun C, Theodoropoulos C, Scrutton NS. Techno-economic assessment of microbial limonene production. Bioresour Technol. 2020;300:122666. https://doi.org/10.1016/j.biortech.2019.122666.
Google Scholar
Yamabe Y, Kawagoe Y, Okuno K, Inoue M, Chikaoka K, Ueda D, et al. Construction of an artificial system for ambrein biosynthesis and investigation of some biological activities of ambrein. Sci Rep. 2020;10(1):19643. https://doi.org/10.1038/s41598-020-76624-y.
Google Scholar
Yeung AWK, Tzvetkov NT, Gupta VK, Gupta SC, Orive G, Bonn GK, et al. Current research in biotechnology: exploring the biotech forefront. Curr Res Biotechnol. 2019;1:34–40. https://doi.org/10.1016/j.crbiot.2019.08.003.
Google Scholar
Kim J, Salvador M, Saunders E, Gonzalez J, Avignone-Rossa C, Jimenez JI. Properties of alternative microbial hosts used in synthetic biology: towards the design of a modular chassis. Essays Biochem. 2016;60(4):303–13. https://doi.org/10.1042/EBC20160015.
Google Scholar
Li G, Liang H, Gao R, Qin L, Xu P, Huang M, et al. Yeast metabolism adaptation for efficient terpenoids synthesis via isopentenol utilization. Nat Commun. 2024;15(1):9844. https://doi.org/10.1038/s41467-024-54298-8.
Google Scholar
Hao Y, Liu M, Fordjour E, Yu P, Yang Y, Liu X, et al. Engineering Escherichia coli for perillyl alcohol production with reduced endogenous dehydrogenation. ACS Synth Biol. 2025. https://doi.org/10.1021/acssynbio.4c00854.
Google Scholar
Cha YP, Li W, Wu T, You X, Chen HF, Zhu CY, et al. Probing the synergistic ratio of P450/CPR to improve (+)-nootkatone production in Saccharomyces cerevisiae. J Agric Food Chem. 2022;70(3):815–25. https://doi.org/10.1021/acs.jafc.1c07035.
Google Scholar
Cheng YT, Luo LL, Tang H, Wang J, Ren L, Cui GH, et al. Engineering the microenvironment of P450s to enhance the production of diterpenoids in Saccharomyces cerevisiae. Acta Pharm Sin B. 2024;14(10):4608–18. https://doi.org/10.1016/j.apsb.2024.05.019.
Google Scholar
Srivastava G, Vyas P, Kumar A, Singh A, Bhargav P, Dinday S, et al. Unraveling the role of cytochrome P450 enzymes in oleanane triterpenoid biosynthesis in arjuna tree. Plant J. 2024;119(6):2687–705. https://doi.org/10.1111/tpj.16942.
Google Scholar
Ma Y, Zu Y, Huang S, Stephanopoulos G. Engineering a universal and efficient platform for terpenoid synthesis in yeast. Proc Natl Acad Sci U S A. 2023;120(1):e2207680120. https://doi.org/10.1073/pnas.2207680120.
Google Scholar
Ganjave SD, Dodia H, Sunder AV, Madhu S, Wangikar PP. High cell density cultivation of E. coli in shake flasks for the production of recombinant proteins. Biotechnol Rep. 2022;33:e00694. https://doi.org/10.1016/j.btre.2021.e00694.
Google Scholar
Teng Y, Jiang T, Yan Y. The expanded CRISPR toolbox for constructing microbial cell factories. Trends Biotechnol. 2024;42(1):104–18. https://doi.org/10.1016/j.tibtech.2023.06.012.
Google Scholar
Khanijou JK, Hee YT, Scipion CPM, Chen X, Selvarajoo K. Systems biology approach for enhancing limonene yield by re-engineering Escherichia coli. NPJ Syst Biol Appl. 2024;10(1):109. https://doi.org/10.1038/s41540-024-00440-7.
Google Scholar
Schuster LA, Reisch CR. Plasmids for controlled and tunable high level expression in E coli. Appl Enviro Microbiol. 2022;88(22):e0093922. https://doi.org/10.1128/aem.00939-22.
Google Scholar
Zong Z, Hua Q, Tong X, Li D, Wang C, Guo D, et al. Biosynthesis of nerol from glucose in the metabolic engineered Escherichia coli. Bioresour Technol. 2019;287:121410. https://doi.org/10.1016/j.biortech.2019.121410.
Google Scholar
Lei D, Qiu Z, Wu J, Qiao B, Qiao J, Zhao GR. Combining metabolic and monoterpene synthase engineering for de Novo production of monoterpene alcohols in Escherichia coli. ACS Synth Biol. 2021;10(6):1531–44. https://doi.org/10.1021/acssynbio.1c00081.
Google Scholar
Liu W, Xu X, Zhang R, Cheng T, Cao Y, Li X, et al. Engineering Escherichia coli for high-yield geraniol production with biotransformation of geranyl acetate to geraniol under fed-batch culture. Biotechnol Biofuels. 2016;9:58. https://doi.org/10.1186/s13068-016-0466-5.
Google Scholar
Wang X, Chen J, Zhang J, Zhou Y, Zhang Y, Wang F, et al. Engineering Escherichia coli for production of geraniol by systematic synthetic biology approaches and laboratory-evolved fusion tags. Metab Eng. 2021;66:60–7. https://doi.org/10.1016/j.ymben.2021.04.008.
Google Scholar
Shukal S, Ong L, T R, Chen X, Zhang C. Microaerobic fermentation enables high-titer biosynthesis of the rose monoterpenes geraniol and geranyl acetate in Escherichia coli. ACS Sustain Chem Eng. 2024;12(10):3921–32. https://doi.org/10.1021/acssuschemeng.3c06030.
Google Scholar
Wu J, Cheng S, Cao J, Qiao J, Zhao GR. Systematic optimization of limonene production in engineered Escherichia coli. J Agric Food Chem. 2019;67(25):7087–97. https://doi.org/10.1021/acs.jafc.9b01427.
Google Scholar
Willrodt C, David C, Cornelissen S, BüHLER B, Julsing MK, Schmid A. Engineering the productivity of recombinant Escherichia coli for limonene formation from glycerol in minimal media. Biotechnol J. 2014;9(8):1000–12. https://doi.org/10.1002/biot.201400023.
Google Scholar
Rolf J, Julsing MK, Rosenthal K, Lutz S. A gram-scale limonene production process with engineered Escherichia coli. Mol. 2020. https://doi.org/10.3390/molecules25081881.
Google Scholar
Weston-Green K, Clunas H, Jimenez Naranjo C. A review of the potential use of pinene and linalool as terpene-based medicines for brain health: discovering novel therapeutics in the flavours and fragrances of cannabis. Front Psychiatry. 2021;12:583211. https://doi.org/10.3389/fpsyt.2021.583211.
Google Scholar
Dickey RM, Gopal MR, Nain P, Kunjapur AM. Recent developments in enzymatic and microbial biosynthesis of flavor and fragrance molecules. J Biotechnol. 2024;389:43–60. https://doi.org/10.1016/j.jbiotec.2024.04.004.
Google Scholar
Bokinsky G, Peralta-Yahya PP, George A, Holmes BM, Steen EJ, Dietrich J, et al. Synthesis of three advanced biofuels from ionic liquid-pretreated switchgrass using engineered Escherichia coli. Proc Natl Acad Sci U S A. 2011;108(50):19949–54. https://doi.org/10.1073/pnas.1106958108.
Google Scholar
Yang J, Nie Q, Ren M, Feng H, Jiang X, Zheng Y, et al. Metabolic engineering of Escherichia coli for the biosynthesis of alpha-pinene. Biotechnol Biofuels. 2013;6(1):60. https://doi.org/10.1186/1754-6834-6-60.
Google Scholar
Sarria S, Wong B, Martín HG, Keasling JD, Peralta-Yahya P. Microbial synthesis of pinene. ACS Synth Biol. 2014;3(7):466–75. https://doi.org/10.1021/sb4001382.
Google Scholar
Huang MY, Wang WY, Liang ZZ, Huang YC, Yi Y, Niu FX. Enhancing the production of pinene in Escherichia coli by using a combination of shotgun, product-tolerance and I-SceI cleavage systems. Biology. 2022;11(10):1484. https://doi.org/10.3390/biology11101484.
Google Scholar
Bao SH, Zhang DY, Meng E. Improving biosynthetic production of pinene through plasmid recombination elimination and pathway optimization. Plasmid. 2019;105:102431. https://doi.org/10.1016/j.plasmid.2019.102431.
Google Scholar
Wei LJ, Zhong YT, Nie MY, Liu SC, Hua Q. Biosynthesis of alpha-Pinene by genetically engineered Yarrowia lipolytica from low-cost renewable feedstocks. J Agric Food Chem. 2021;69(1):275–85. https://doi.org/10.1021/acs.jafc.0c06504.
Google Scholar
Niu FX, Huang YB, Shen YP, Ji LN, Liu JZ. Enhanced production of pinene by using a cell-free system with modular cocatalysis. J Agric Food Chem. 2020;68(7):2139–45. https://doi.org/10.1021/acs.jafc.9b07830.
Google Scholar
Dunlop MJ, Dossani ZY, Szmidt HL, Chu HC, Lee TS, Keasling JD, et al. Engineering microbial biofuel tolerance and export using efflux pumps. Mol Syst Biol. 2011;7(1):487. https://doi.org/10.1038/msb.2011.21.
Google Scholar
Su P, Hu T, Liu Y, Tong Y, Guan H, Zhang Y, et al. Functional characterization of NES and GES responsible for the biosynthesis of (E)-nerolidol and (E,E)-geranyllinalool in Tripterygium wilfordii. Sci Rep. 2017;7:40851. https://doi.org/10.1038/srep40851.
Google Scholar
Peng B, Plan MR, Chrysanthopoulos P, Hodson MP, Nielsen LK, Vickers CE. A squalene synthase protein degradation method for improved sesquiterpene production in Saccharomyces cerevisiae. Metab Eng. 2017;39:209–19. https://doi.org/10.1016/j.ymben.2016.12.003.
Google Scholar
Li W, Zhang W, Liu Z, Song H, Wang S, Zhang Y, et al. Review of recent advances in microbial production and applications of nerolidol. J Agric Food Chem. 2025;73(10):5724–47. https://doi.org/10.1021/acs.jafc.4c12579.
Google Scholar
Tan N, Ong L, Shukal S, Chen X, Zhang C. High-yield biosynthesis of trans-nerolidol from sugar and glycerol. J Agric Food Chem. 2023;71(22):8479–87. https://doi.org/10.1021/acs.jafc.3c01161.
Google Scholar
Wang C, Park JE, Choi ES, Kim SW. Farnesol production in Escherichia coli through the construction of a farnesol biosynthesis pathway – application of PgpB and YbjG phosphatases. Biotechnol J. 2016;11(10):1291–7. https://doi.org/10.1002/biot.201600250.
Google Scholar
Kong S, Fu X, Li X, Pan H, Guo D. De novo biosynthesis of linalool from glucose in engineered Escherichia coli. Enzyme Microb Technol. 2020;140:109614. https://doi.org/10.1016/j.enzmictec.2020.109614.
Google Scholar
Wu J, Wang X, Xiao L, Wang F, Zhang Y, Li X. Synthetic protein scaffolds for improving R-(-)-linalool production in Escherichia coli. J Agric Food Chem. 2021;69(20):5663–70. https://doi.org/10.1021/acs.jafc.1c01101.
Google Scholar
Wang X, Zhang X, Zhang J, Xiao L, Zhou Y, Wang F, et al. Metabolic engineering of Escherichia coli for efficient production of linalool from biodiesel-derived glycerol by targeting cofactors regeneration and reducing acetate accumulation. Ind Crops Prod. 2023;203:117152. https://doi.org/10.1016/j.indcrop.2023.117152.
Google Scholar
Li X, Ren JN, Fan G, Zhang LL, Pan SY. Advances on (+)-nootkatone microbial biosynthesis and its related enzymes. J Ind Microbiol Biotechnol. 2021. https://doi.org/10.1093/jimb/kuab046.
Google Scholar
Girhard M, Machida K, Itoh M, Schmid RD, Arisawa A, Urlacher VB. Regioselective biooxidation of (+)-valencene by recombinant E. coli expressing CYP109B1 from Bacillus subtilis in a two-liquid-phase system. Microb Cell Fact. 2009;8(1):36. https://doi.org/10.1186/1475-2859-8-36.
Google Scholar
Chang J, Wei X, Liu D, Li Q, Li C, Zhao J, et al. Engineering Escherichia coli via introduction of the isopentenol utilization pathway to effectively produce geranyllinalool. Microb Cell Fact. 2024;23(1):292. https://doi.org/10.1186/s12934-024-02563-2.
Google Scholar
Schalk M, Pastore L, Mirata MA, Khim S, Schouwey M, Deguerry F, et al. Toward a biosynthetic route to sclareol and amber odorants. J Am Chem Soc. 2012;134(46):18900–3. https://doi.org/10.1021/ja307404u.
Google Scholar
Cheng T, Zhao G, Xian M, Xie C. Improved cis-Abienol production through increasing precursor supply in Escherichia coli. Sci Rep. 2020;10(1):16791. https://doi.org/10.1038/s41598-020-73934-z.
Google Scholar
Li L, Wang X, Li X, Shi H, Wang F, Zhang Y, et al. Combinatorial engineering of mevalonate pathway and diterpenoid synthases in Escherichia coli for cis-abienol production. J Agric Food Chem. 2019;67(23):6523–31. https://doi.org/10.1021/acs.jafc.9b02156.
Google Scholar
Zhang X, Zhu K, Shi H, Wang X, Zhang Y, Wang F, et al. Engineering Escherichia coli for effective and economic production of cis-abienol by optimizing isopentenol utilization pathway. J Clean Prod. 2022;351:131310. https://doi.org/10.1016/j.jclepro.2022.131310.
Google Scholar
Yang H, Zhang K, Shen W, Chen L, Xia Y, Zou W, et al. Efficient production of cembratriene-ol in Escherichia coli via systematic optimization. Microb Cell Fact. 2023;22(1):17. https://doi.org/10.1186/s12934-023-02022-4.
Google Scholar
Schrepfer P, Ugur I, Klumpe S, Loll B, Kaila VRI, Bruck T. Exploring the catalytic cascade of cembranoid biosynthesis by combination of genetic engineering and molecular simulations. Comput Struct Biotechnol J. 2020;18:1819–29. https://doi.org/10.1016/j.csbj.2020.06.030.
Google Scholar
Wang G, Wei X, Li Q, Chang J, Yang X. Metabolic engineering of Escherichia coli for enhanced production of cembratrien-ols via precursor supply optimization and membrane engineering. J Agric Food Chem. 2025. https://doi.org/10.1021/acs.jafc.5c01254.
Google Scholar
Ke D, Caiyin Q, Zhao F, Liu T, Lu W. Heterologous biosynthesis of triterpenoid ambrein in engineered Escherichia coli. Biotechnol Lett. 2018;40(2):399–404. https://doi.org/10.1007/s10529-017-2483-2.
Google Scholar
Naseri G. A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast. Nat Commun. 2023;14(1):1916. https://doi.org/10.1038/s41467-023-37627-1.
Google Scholar
Lee H, Song J, Seo SW. Engineering Yarrowia lipolytica for the production of beta-carotene by carbon and redox rebalancing. J Biol Eng. 2025;19(1):6. https://doi.org/10.1186/s13036-025-00476-1.
Google Scholar
Zhou K, Yu C, Liang N, Xiao W, Wang Y, Yao M, et al. Adaptive evolution and metabolic engineering boost lycopene production in Saccharomyces cerevisiae via enhanced precursors supply and utilization. J Agric Food Chem. 2023;71(8):3821–31. https://doi.org/10.1021/acs.jafc.2c08579.
Google Scholar
Bureau JA, Oliva ME, Dong Y, Ignea C. Engineering yeast for the production of plant terpenoids using synthetic biology approaches. Nat Prod Rep. 2023;40(12):1822–48. https://doi.org/10.1039/d3np00005b.
Google Scholar
Zhou P, Du Y, Xu N, Yue C, Ye L. Improved linalool production in Saccharomyces cerevisiae by combining directed evolution of linalool synthase and overexpression of the complete mevalonate pathway. Biochem Eng J. 2020;161:107655. https://doi.org/10.1016/j.bej.2020.107655.
Google Scholar
Zhou P, Du Y, Fang X, Xu N, Yue C, Ye L. Combinatorial modulation of linalool synthase and farnesyl diphosphate synthase for linalool overproduction in Saccharomyces cerevisiae. J Agric Food Chem. 2021;69(3):1003–10. https://doi.org/10.1021/acs.jafc.0c06384.
Google Scholar
Zhang Y, Cao X, Wang J, Tang F. Enhancement of linalool production in Saccharomyces cerevisiae by utilizing isopentenol utilization pathway. Microb Cell Fact. 2022;21(1):212. https://doi.org/10.1186/s12934-022-01934-x.
Google Scholar
Zhang C, Li M, Zhao GR, Lu W. Alpha-terpineol production from an engineered Saccharomyces cerevisiae cell factory. Microb Cell Fact. 2019;18(1):160. https://doi.org/10.1186/s12934-019-1211-0.
Google Scholar
Zhao J, Bao X, Li C, Shen Y, Hou J. Improving monoterpene geraniol production through geranyl diphosphate synthesis regulation in Saccharomyces cerevisiae. Appl Microbiol Biotechnol. 2016;100(10):4561–71. https://doi.org/10.1007/s00253-016-7375-1.
Google Scholar
Zhao C, Wang XH, Lu XY, Zong H, Zhuge B. Tuning geraniol biosynthesis via a novel decane-responsive promoter in Candida glycerinogenes. ACS Synth Biol. 2022;11(5):1835–44. https://doi.org/10.1021/acssynbio.2c00003.
Google Scholar
Zhao C, Wang XH, Lu XY, Zong H, Zhuge B. Metabolic engineering of Candida glycerinogenes for sustainable production of geraniol. ACS Synth Biol. 2023;12(6):1836–44. https://doi.org/10.1021/acssynbio.3c00195.
Google Scholar
Chen Y, Daviet L, Schalk M, Siewers V, Nielsen J. Establishing a platform cell factory through engineering of yeast acetyl-CoA metabolism. Metab Eng. 2013;15:48–54. https://doi.org/10.1016/j.ymben.2012.11.002.
Google Scholar
Scalcinati G, Knuf C, Partow S, Chen Y, Maury J, Schalk M, et al. Dynamic control of gene expression in engineered for the production of plant sesquitepene α-santalene in a fed-batch mode. Metab Eng. 2012;14(2):91–103. https://doi.org/10.1016/j.ymben.2012.01.007.
Google Scholar
Zha W, An T, Li T, Zhu J, Gao K, Sun Z, et al. Reconstruction of the biosynthetic pathway of santalols under control of the GAL regulatory system in yeast. ACS Synth Biol. 2020;9(2):449–56. https://doi.org/10.1021/acssynbio.9b00479.
Google Scholar
Zhang J, Wang X, Zhang X, Zhang Y, Wang F, Li X. Sesquiterpene synthase engineering and targeted engineering of alpha-santalene overproduction in Escherichia coli. J Agric Food Chem. 2022;70(17):5377–85. https://doi.org/10.1021/acs.jafc.2c00754.
Google Scholar
Qu Z, Zhang L, Zhu S, Yuan W, Hang J, Yin D, et al. Overexpression of the transcription factor HAC1 improves nerolidol production in engineered yeast. Enzyme Microb Technol. 2020;134:109485. https://doi.org/10.1016/j.enzmictec.2019.109485.
Google Scholar
Li W, Yan X, Zhang Y, Liang D, Caiyin Q, Qiao J. Characterization of trans-Nerolidol synthase from Celastrus angulatus Maxim and production of trans-Nerolidol in engineered Saccharomyces cerevisiae. J Agric Food Chem. 2021;69(7):2236–44. https://doi.org/10.1021/acs.jafc.0c06084.
Google Scholar
Sabulal B, Dan M, J AJ, Kurup R, Pradeep NS, Valsamma RK, et al. Caryophyllene-rich rhizome oil of Zingiber nimmonii from South India: chemical characterization and antimicrobial activity. Phytochemistry. 2006;67(22):2469–73. https://doi.org/10.1016/j.phytochem.2006.08.003.
Google Scholar
Styger G, Prior B, Bauer FF. Wine flavor and aroma. J Ind Microbiol Biotechnol. 2011;38(9):1145–59. https://doi.org/10.1007/s10295-011-1018-4.
Google Scholar
Harvey BG, Meylemans HA, Gough RV, Quintana RL, Garrison MD, Bruno TJ. High-density biosynthetic fuels: the intersection of heterogeneous catalysis and metabolic engineering. Phys Chem Chem Phys. 2014;16(20):9448–57. https://doi.org/10.1039/c3cp55349c.
Google Scholar
Lu S, Deng H, Zhou C, Du Z, Guo X, Cheng Y, et al. Enhancement of beta-caryophyllene biosynthesis in Saccharomyces cerevisiae via synergistic evolution of beta-caryophyllene synthase and engineering the chassis. ACS Synth Biol. 2023;12(6):1696–707. https://doi.org/10.1021/acssynbio.3c00024.
Google Scholar
Cheng T, Zhang K, Guo J, Yang Q, Li Y, Xian M, et al. Highly efficient biosynthesis of beta-caryophyllene with a new sesquiterpene synthase from tobacco. Biotechnol Biofuels Bioprod. 2022;15(1):39. https://doi.org/10.1186/s13068-022-02136-8.
Google Scholar
Yang J, Li Z, Guo L, Du J, Bae H-J. Biosynthesis of β-caryophyllene, a novel terpene-based high-density biofuel precursor, using engineered Escherichia coli. Renew Energy. 2016;99:216–23. https://doi.org/10.1016/j.renene.2016.06.061.
Google Scholar
Gietz RD, Schiestl RH. High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat Protoc. 2007;2(1):31–4. https://doi.org/10.1038/nprot.2007.13.
Google Scholar
Li Z, Gan Y, Gou C, Ye Q, Wu Y, Wu Y, et al. Efficient biosynthesis of beta-caryophyllene in Saccharomyces cerevisiae by beta-caryophyllene synthase from Artemisia argyi. Synth Syst Biotechnol. 2025;10(1):158–64. https://doi.org/10.1016/j.synbio.2024.09.005.
Google Scholar
Zhang Y, Liu C, Li W, Ma Z, Lv B, Qin L, et al. Systematic engineering of the sterol synthesis pathway for Saccharomyces cerevisiae promotes the efficient production of β-caryophyllene. Metab Eng. 2025;91:347–55. https://doi.org/10.1016/j.ymben.2025.06.004.
Google Scholar
Wang J, Zhu L, Li Y, Xu S, Jiang W, Liang C, et al. Enhancing geranylgeraniol production by metabolic engineering and utilization of isoprenol as a substrate in Saccharomyces cerevisiae. J Agric Food Chem. 2021;69(15):4480–9. https://doi.org/10.1021/acs.jafc.1c00508.
Google Scholar
Wang K, Yin M, Sun ML, Zhao Q, Ledesma-Amaro R, Ji XJ, et al. Engineering Yarrowia lipolytica for efficient synthesis of geranylgeraniol. J Agric Food Chem. 2024;72(37):20568–81. https://doi.org/10.1021/acs.jafc.4c06749.
Google Scholar
Wang J, Li Y, Jiang W, Hu J, Gu Z, Xu S, et al. Engineering Saccharomyces cerevisiae YPH499 for overproduction of geranylgeraniol. J Agric Food Chem. 2023;71(25):9804–14. https://doi.org/10.1021/acs.jafc.3c01820.
Google Scholar
Ouyang X, Cha Y, Li W, Zhu C, Zhu M, Li S, et al. Stepwise engineering of Saccharomyces cerevisiae to produce (+)-valencene and its related sesquiterpenes. RSC Adv. 2019;9(52):30171–81. https://doi.org/10.1039/c9ra05558d.
Google Scholar
Liu T, Li W, Chen H, Wu T, Zhu C, Zhuo M, et al. Systematic optimization of HPO-CPR to boost (+)-nootkatone synthesis in engineered Saccharomyces cerevisiae. J Agric Food Chem. 2022;70(49):15548–59. https://doi.org/10.1021/acs.jafc.2c07068.
Google Scholar
Sun M-L, Han Y, Yu X, Wang K, Lin L, Ledesma-Amaro R, et al. Constructing a green oleaginous yeast cell factory for sustainable production of the plant-derived diterpenoid sclareol. Green Chem. 2024;26(9):5202–10. https://doi.org/10.1039/D3GC04949C.
Google Scholar
Cao X, Yu W, Chen Y, Yang S, Zhao ZK, Nielsen J, et al. Engineering yeast for high-level production of diterpenoid sclareol. Metab Eng. 2023;75:19–28. https://doi.org/10.1016/j.ymben.2022.11.002.
Google Scholar
Moser S, Strohmeier GA, Leitner E, Plocek TJ, Vanhessche K, Pichler H. Whole-cell (+)-ambrein production in the yeast Pichia pastoris. Metab Eng Commun. 2018;7:e00077. https://doi.org/10.1016/j.mec.2018.e00077.
Google Scholar
Lin C, Zhang X, Ji Z, Fan B, Chen Y, Wu Y, et al. Metabolic engineering of Saccharomyces cerevisiae for high-level production of (+)-ambrein from glucose. Biotechnol Lett. 2024;46(4):615–26. https://doi.org/10.1007/s10529-024-03502-2.
Google Scholar
Kapoor L, Ramamoorthy S. Strategies to meet the global demand for natural food colorant bixin: a multidisciplinary approach. J Biotechnol. 2021;338:40–51. https://doi.org/10.1016/j.jbiotec.2021.07.007.
Google Scholar
Debnath T, Bandyopadhyay TK, Vanitha K, Bobby MN, Nath Tiwari O, Bhunia B, et al. Astaxanthin from microalgae: a review on structure, biosynthesis, production strategies and application. Food Res Int. 2024;176:113841. https://doi.org/10.1016/j.foodres.2023.113841.
Google Scholar
Cao K, Cui Y, Sun F, Zhang H, Fan J, Ge B, et al. Metabolic engineering and synthetic biology strategies for producing high-value natural pigments in microalgae. Biotechnol Adv. 2023;68:108236. https://doi.org/10.1016/j.biotechadv.2023.108236.
Google Scholar
Cataldo VF, Lopez J, Carcamo M, Agosin E. Chemical vs. biotechnological synthesis of C13-apocarotenoids: current methods, applications and perspectives. Appl Microbiol Biotechnol. 2016;100(13):5703–18. https://doi.org/10.1007/s00253-016-7583-8.
Google Scholar
Lin P, Zhang L, Du G, Chen J, Zhang J, Peng Z. Construction of Saccharomyces cerevisiae platform strain for the biosynthesis of carotenoids and apocarotenoids. J Agric Food Chem. 2025;73(15):9187–96. https://doi.org/10.1021/acs.jafc.5c00088.
Google Scholar
Ma Y, Liu N, Greisen P, Li J, Qiao K, Huang S, et al. Removal of lycopene substrate inhibition enables high carotenoid productivity in Yarrowia lipolytica. Nat Commun. 2022;13(1):572. https://doi.org/10.1038/s41467-022-28277-w.
Google Scholar
Bian Q, Zhou P, Yao Z, Li M, Yu H, Ye L. Heterologous biosynthesis of lutein in S. cerevisiae enabled by temporospatial pathway control. Metab Eng. 2021;67:19–28. https://doi.org/10.1016/j.ymben.2021.05.008.
Google Scholar
Kim GB, Kim HR, Lee SY. Comprehensive evaluation of the capacities of microbial cell factories. Nat Commun. 2025;16(1):2869. https://doi.org/10.1038/s41467-025-58227-1.
Google Scholar
Peng B, Wei S. Synthetic engineering of microbes for production of terpenoid food ingredients. J Agric Food Chem. 2025. https://doi.org/10.1021/acs.jafc.5c01724.
Google Scholar
Han T, Nazarbekov A, Zou X, Lee SY. Recent advances in systems metabolic engineering. Curr Opin Biotechnol. 2023;84:103004. https://doi.org/10.1016/j.copbio.2023.103004.
Google Scholar
Tan JC, Hu Q, Scrutton NS. A growth-coupling strategy for improving the stability of terpenoid bioproduction in Escherichia coli. Microb Cell Fact. 2024;23(1):279. https://doi.org/10.1186/s12934-024-02548-1.
Google Scholar
Diaz JE, Lin CS, Kunishiro K, Feld BK, Avrantinis SK, Bronson J, et al. Computational design and selections for an engineered, thermostable terpene synthase. Protein Sci. 2011;20(9):1597–606. https://doi.org/10.1002/pro.691.
Google Scholar
Woolston BM, Edgar S, Stephanopoulos G. Metabolic engineering: past and future. Annu Rev Chem Biomol Eng. 2013;4(1):259–88. https://doi.org/10.1146/annurev-chembioeng-061312-103312.
Google Scholar
Zhang C, Chen X, Lindley ND, Too HP. A “plug-n-play” modular metabolic system for the production of apocarotenoids. Biotechnol Bioeng. 2018;115(1):174–83. https://doi.org/10.1002/bit.26462.
Google Scholar
Lu Y, Yang Q, Lin Z, Yang X. A modular pathway engineering strategy for the high-level production of beta-ionone in Yarrowia lipolytica. Microb Cell Fact. 2020;19(1):49. https://doi.org/10.1186/s12934-020-01309-0.
Google Scholar
Eauclaire SF, Zhang J, Rivera CG, Huang LL. Combinatorial metabolic pathway assembly in the yeast genome with RNA-guided Cas9. J Ind Microbiol Biotechnol. 2016;43(7):1001–15. https://doi.org/10.1007/s10295-016-1776-0.
Google Scholar
Lian J, Hamedirad M, Hu S, Zhao H. Combinatorial metabolic engineering using an orthogonal tri-functional CRISPR system. Nat Commun. 2017;8(1):1688. https://doi.org/10.1038/s41467-017-01695-x.
Google Scholar
Zhang XK, Wang DN, Chen J, Liu ZJ, Wei LJ, Hua Q. Metabolic engineering of β-carotene biosynthesis in Yarrowia lipolytica. Biotechnol Lett. 2020;42(6):945–56. https://doi.org/10.1007/s10529-020-02844-x.
Google Scholar
Zhang Y, Ma L, Su P, Huang L, Gao W. Cytochrome P450s in plant terpenoid biosynthesis: discovery, characterization and metabolic engineering. Crit Rev Biotechnol. 2023;43(1):1–21. https://doi.org/10.1080/07388551.2021.2003292.
Google Scholar
Bilal M, Iqbal HMN. Tailoring multipurpose biocatalysts via protein engineering approaches: a review. Catal Lett. 2019;149(8):2204–17. https://doi.org/10.1007/s10562-019-02821-8.
Google Scholar
Park SY, Eun H, Lee MH, Lee SY. Metabolic engineering of Escherichia coli with electron channelling for the production of natural products. Nat Catal. 2022;5(8):726–37. https://doi.org/10.1038/s41929-022-00820-4.
Google Scholar
Kang W, Ma X, Kakarla D, Zhang H, Fang Y, Chen B, et al. Organizing enzymes on self-assembled protein cages for cascade reactions. Angew Chem Int Ed Engl. 2022;61(52):e202214001. https://doi.org/10.1002/anie.202214001.
Google Scholar
Wu T, Ye L, Zhao D, Li S, Li Q, Zhang B, et al. Membrane engineering – a novel strategy to enhance the production and accumulation of β-carotene in Escherichia coli. Metab Eng. 2017;43(Pt A):85–91. https://doi.org/10.1016/j.ymben.2017.07.001.
Google Scholar
Sun ZJ, Lian JZ, Zhu L, Jiang YQ, Li GS, Xue HL, et al. Combined biosynthetic pathway engineering and storage pool expansion for high-level production of ergosterol in industrial Saccharomyces cerevisiae. Front Bioeng Biotechnol. 2021;9:681666. https://doi.org/10.3389/fbioe.2021.681666.
Google Scholar
Guo XJ, Yao MD, Xiao WH, Wang Y, Zhao GR, Yuan YJ. Compartmentalized reconstitution of post-squalene pathway for 7-dehydrocholesterol overproduction in Saccharomyces cerevisiae. Front Microbiol. 2021;12:663973. https://doi.org/10.3389/fmicb.2021.663973.
Google Scholar
Shi Y, Wang D, Li R, Huang L, Dai Z, Zhang X. Engineering yeast subcellular compartments for increased production of the lipophilic natural products ginsenosides. Metab Eng. 2021;67:104–11. https://doi.org/10.1016/j.ymben.2021.06.002.
Google Scholar
Wang D, Wang J, Shi Y, Li R, Fan F, Huang Y, et al. Elucidation of the complete biosynthetic pathway of the main triterpene glycosylation products of Panax notoginseng using a synthetic biology platform. Metab Eng. 2020;61:131–40. https://doi.org/10.1016/j.ymben.2020.05.007.
Google Scholar
Choi BH, Kang HJ, Kim SC, Lee PC. Organelle engineering in yeast: enhanced production of Protopanaxadiol through manipulation of peroxisome proliferation in Saccharomyces cerevisiae. Microorganisms. 2022. https://doi.org/10.3390/microorganisms10030650.
Google Scholar
Du MM, Zhu ZT, Zhang GG, Zhao YQ, Gao B, Tao XY, et al. Engineering Saccharomyces cerevisiae for hyperproduction of beta-amyrin by mitigating the inhibition effect of squalene on beta-amyrin synthase. J Agric Food Chem. 2022;70(1):229–37. https://doi.org/10.1021/acs.jafc.1c06712.
Google Scholar
Dong C, Shi Z, Huang L, Zhao H, Xu Z, Lian J. Cloning and characterization of a panel of mitochondrial targeting sequences for compartmentalization engineering in Saccharomyces cerevisiae. Biotechnol Bioeng. 2021;118(11):4269–77. https://doi.org/10.1002/bit.27896.
Google Scholar
Yao Z, Zhou P, Su B, Su S, Ye L, Yu H. Enhanced isoprene production by reconstruction of metabolic balance between strengthened precursor supply and improved isoprene synthase in Saccharomyces cerevisiae. ACS Synth Biol. 2018;7(9):2308–16. https://doi.org/10.1021/acssynbio.8b00289.
Google Scholar
Fordjour E, Mensah EO, Hao Y, Yang Y, Liu X, Li Y, et al. Toward improved terpenoids biosynthesis: strategies to enhance the capabilities of cell factories. Bioresour Bioprocess. 2022;9(1):6. https://doi.org/10.1186/s40643-022-00493-8.
Google Scholar
Bu X, Lin JY, Cheng J, Yang D, Duan CQ, Koffas M, et al. Engineering endogenous ABC transporter with improving ATP supply and membrane flexibility enhances the secretion of beta-carotene in Saccharomyces cerevisiae. Biotechnol Biofuels. 2020;13:168. https://doi.org/10.1186/s13068-020-01809-6.
Google Scholar
Wu T, Li S, Ye L, Zhao D, Fan F, Li Q, et al. Engineering an artificial membrane vesicle trafficking system (AMVTS) for the excretion of beta-carotene in Escherichia coli. ACS Synth Biol. 2019;8(5):1037–46. https://doi.org/10.1021/acssynbio.8b00472.
Google Scholar
Matsumoto T, Osawa T, Taniguchi H, Saito A, Yamada R, Ogino H. Mitochondrial expression of metabolic enzymes for improving carotenoid production in Saccharomyces cerevisiae. Biochem Eng J. 2022;189:108720. https://doi.org/10.1016/j.bej.2022.108720.
Google Scholar
Dusseaux S, Wajn WT, Liu Y, Ignea C, Kampranis SC. Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids. Proc Natl Acad Sci U S A. 2020;117(50):31789–99. https://doi.org/10.1073/pnas.2013968117.
Google Scholar
Baker JJ, Shi J, Wang S, Mujica EM, Bianco S, Capponi S, et al. ML-enhanced peroxisome capacity enables compartmentalization of multienzyme pathway. Nat Chem Biol. 2024. https://doi.org/10.1038/s41589-024-01759-2.
Google Scholar
Niu FX, He X, Wu YQ, Liu JZ. Enhancing production of pinene in Escherichia coli by using a combination of tolerance, evolution, and modular co-culture engineering. Front Microbiol. 2018;9:1623. https://doi.org/10.3389/fmicb.2018.01623.
Google Scholar
Zhu C, You X, Wu T, Li W, Chen H, Cha Y, et al. Efficient utilization of carbon to produce aromatic valencene in Saccharomyces cerevisiae using mannitol as the substrate. Green Chem. 2022;24(11):4614–27. https://doi.org/10.1039/d2gc00867j.
Google Scholar
Li J, Zhu K, Miao L, Rong L, Zhao Y, Li S, et al. Simultaneous improvement of limonene production and tolerance in Yarrowia lipolytica through tolerance engineering and evolutionary engineering. ACS Synth Biol. 2021;10(4):884–96. https://doi.org/10.1021/acssynbio.1c00052.
Google Scholar
Karlova R, Busscher J, Schempp FM, Buchhaupt M, VAN Dijk ADJ, Beekwilder J. Detoxification of monoterpenes by a family of plant glycosyltransferases. Phytochem. 2022. https://doi.org/10.1016/j.phytochem.2022.113371.
Google Scholar
Rinaldi MA, Ferraz CA, Scrutton NS. Alternative metabolic pathways and strategies to high-titre terpenoid production in Escherichia coli. Nat Prod Rep. 2022;39(1):90–118. https://doi.org/10.1039/d1np00025j.
Google Scholar
Priebe X, Hoang MD, Rudiger J, Turgel M, Trondle J, Schwab W, et al. Byproduct-free geraniol glycosylation by whole-cell biotransformation with recombinant Escherichia coli. Biotechnol Lett. 2021;43(1):247–59. https://doi.org/10.1007/s10529-020-02993-z.
Google Scholar
Wang X, Zhang X, Zhang J, Xiao L, Zhou Y, Zhang Y, et al. Genetic and bioprocess engineering for the selective and high-level production of geranyl acetate in Escherichia coli. ACS Sustain Chem Eng. 2022;10(9):2881–9. https://doi.org/10.1021/acssuschemeng.1c07336.
Google Scholar
He N, Li D-F, Yu H-W, Ye L-D. Construction of an artificial microbial consortium for green production of (−)-ambroxide. ACS Sustain Chem Eng. 2023;11(5):1939–48. https://doi.org/10.1021/acssuschemeng.2c06716.
Google Scholar
Qi Z, Tong X, Ke K, Wang X, Pei J, Bu S, et al. De novo synthesis of dihydro-beta-ionone through metabolic engineering and bacterium-yeast coculture. J Agric Food Chem. 2024;72(6):3066–76. https://doi.org/10.1021/acs.jafc.3c07291.
Google Scholar
Tang D, Zheng X, Zhao Y, Zhang C, Chen C, Chen Y, et al. Engineered microbial consortium for de novo production of Sclareolide. J Agric Food Chem. 2024;72(36):19977–84. https://doi.org/10.1021/acs.jafc.4c05506.
Google Scholar
Nadal-Rey G, Mcclure DD, Kavanagh JM, Cornelissen S, Fletcher DF, Gernaey KV. Understanding gradients in industrial bioreactors. Biotechnol Adv. 2021;46:107660. https://doi.org/10.1016/j.biotechadv.2020.107660.
Google Scholar
Kuschel M, Takors R. Simulated oxygen and glucose gradients as a prerequisite for predicting industrial scale performance a priori. Biotechnol Bioeng. 2020;117(9):2760–70. https://doi.org/10.1002/bit.27457.
Google Scholar
Huang CN, Lim X, Ong L, Lim C, Chen X, Zhang C. Mediating oxidative stress enhances alpha-ionone biosynthesis and strain robustness during process scaling up. Microb Cell Fact. 2022;21(1):246. https://doi.org/10.1186/s12934-022-01968-1.
Google Scholar
Chen M, Li M, Ye L, Yu H. Construction of canthaxanthin-producing yeast by combining spatiotemporal regulation and pleiotropic drug resistance engineering. ACS Synth Biol. 2022;11(1):325–33. https://doi.org/10.1021/acssynbio.1c00437.
Google Scholar
Kang MK, Yoon SH, Kwon M, Kim SW. Microbial cell factories for bio-based isoprenoid production to replace fossil resources. Curr Opin Syst Biol. 2024. https://doi.org/10.1016/j.coisb.2023.100502.
Google Scholar
Sun C, Zhang R, Xie C. Biosynthesis of (R)-(+)-perillyl alcohol by Escherichia coli expressing neryl pyrophosphate synthase. Eng Life Sci. 2022;22(5):407–16. https://doi.org/10.1002/elsc.202100135.
Google Scholar
Wang X, Wang J, Zhang X, Zhang J, Zhou Y, Wang F, et al. Efficient myrcene production using linalool dehydratase isomerase and rational biochemical process in Escherichia coli. J Biotechnol. 2023;371:33–40. https://doi.org/10.1016/j.jbiotec.2023.05.008.
Google Scholar
Lim HS, Kim SK, Woo SG, Kim TH, Yeom SJ, Yong W, et al. (-)-alpha-bisabolol production in engineered Escherichia coli expressing a novel (-)-alpha-bisabolol synthase from the globe artichoke cynara cardunculus var scolymus. J Agric Food Chem. 2021;69(30):8492–503. https://doi.org/10.1021/acs.jafc.1c02759.
Google Scholar
Sun Y, Wu S, Fu X, Lai C, Guo D. De novo biosynthesis of tau-cadinol in engineered Escherichia coli. Bioresour Bioprocess. 2022;9(1):29. https://doi.org/10.1186/s40643-022-00521-7.
Google Scholar
Fordjour E, Liu CL, Hao Y, Sackey I, Yang Y, Liu X, et al. Engineering Escherichia coli BL21 (DE3) for high‐yield production of germacrene A, a precursor of β‐elemene via combinatorial metabolic engineering strategies. Biotechnol Bioeng. 2023;120(10):3039–56. https://doi.org/10.1002/bit.28467.
Google Scholar
Zhou L, Wang Y, Han L, Wang Q, Liu H, Cheng P, et al. Enhancement of patchoulol production in Escherichia coli via multiple engineering strategies. J Agric Food Chem. 2021;69(27):7572–80. https://doi.org/10.1021/acs.jafc.1c02399.
Google Scholar
Zhang H, Cai P, Guo J, Gao J, Xie L, Su P, et al. Engineering cellular dephosphorylation boosts (+)-borneol production in yeast. Acta Pharm Sin B. 2025;15(2):1171–82. https://doi.org/10.1016/j.apsb.2024.12.039.
Google Scholar
Jiang G, Yao M, Wang Y, Xiao W, Yuan Y. A “push-pull-restrain” strategy to improve citronellol production in Saccharomyces cerevisiae. Metab Eng. 2021;66:51–9. https://doi.org/10.1016/j.ymben.2021.03.019.
Google Scholar
Liu J, Chen C, Wan X, Yao G, Bao S, Wang F, et al. Identification of the sesquiterpene synthase AcTPS1 and high production of (-)-germacrene D in metabolically engineered Saccharomyces cerevisiae. Microb Cell Fact. 2022;21(1):89. https://doi.org/10.1186/s12934-022-01814-4.
Google Scholar
Liu M, Lin YC, Guo JJ, Du MM, Tao X, Gao B, et al. High-level production of sesquiterpene patchoulol in Saccharomyces cerevisiae. ACS Synth Biol. 2021;10(1):158–72. https://doi.org/10.1021/acssynbio.0c00521.
Google Scholar
Feng P, Sun B, Bi H, Bao Y, Wang M, Zhang H, et al. Developing thermosensitive metabolic regulation strategies in the fermentation process of Saccharomyces cerevisiae to enhance alpha-bisabolene production. ACS Synth Biol. 2025;14(4):1129–41. https://doi.org/10.1021/acssynbio.4c00728.
Google Scholar
Zhang Y, Bian S, Liu X, Fang N, Wang C, Liu Y, et al. Synthesis of cembratriene-ol and cembratriene-diol in yeast via the MVA pathway. Microb Cell Fact. 2021;20(1):29. https://doi.org/10.1186/s12934-021-01523-4.
Google Scholar