Advances in the sustainable biosynthesis of valuable terpenoid flavor compounds and precursors in micro-organisms | Biotechnology for Biofuels and Bioproducts

  • 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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 

    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.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Continue Reading