{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:11:43Z","timestamp":1790093503268,"version":"4.0.1"},"reference-count":92,"publisher":"American Chemical Society (ACS)","issue":"37","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32570149"],"award-info":[{"award-number":["32570149"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sclareol, a plant-derived diterpene, holds significant industrial value in perfumery, pharmaceuticals, and agriculture. Traditional production from Salvia sclarea or chemical synthesis has faced challenges such as low yield, high cost, and sustainability concerns. Recent advances in synthetic biology and metabolic engineering have enabled sclareol biosynthesis in microbial chassis cells. This Review systematically examines synthetic biology-driven strategies for improving sclareol production, with particular emphasis on microbial chassis engineering, metabolic pathway optimization, and enzyme engineering. Emerging approaches such as AI-assisted prediction, multiomics analysis, high-throughput screening, and intelligent fermentation technologies are also highlighted. Achievements and challenges in microbial sclareol biosynthesis are critically analyzed, and strategic priorities for future development are proposed. This paper provides a comprehensive reference for science and practice, aiming to advance the sustainable biomanufacturing of high-value plant-derived terpenoids.<\/jats:p>","DOI":"10.1021\/acsomega.6c07601","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:01:38Z","timestamp":1788775298000},"page":"54870-54885","source":"Crossref","is-referenced-by-count":0,"title":["Sclareol Production\nDriven by Advanced Synthetic Biology\nStrategies"],"prefix":"10.1021","volume":"11","author":[{"given":"Yiwen","family":"Yu","sequence":"first","affiliation":[{"name":"Hubei University of Technology , , ,","place":["Wuhan, China, 430068"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei University of Technology , , ,","place":["Wuhan, China, 430068"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei University of Technology , , ,","place":["Wuhan, China, 430068"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Qilu Hospital of Shandong University Dezhou Hospital , , ,","place":["Dezhou, China, 253000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamer Ali","family":"Shah","sequence":"additional","affiliation":[{"name":"Quaid-i-Azam University , , ,","place":["Islamabad, Pakistan, 45320"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-6342","authenticated-orcid":true,"given":"Chunjie","family":"Gong","sequence":"additional","affiliation":[{"name":"Hubei University of Technology , , ,","place":["Wuhan, China, 430068"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026092211025750100_cit1","doi-asserted-by":"publisher","first-page":"11570","DOI":"10.1021\/acs.chemrev.7b00287","article-title":"Structural\nand Chemical Biology of Terpenoid Cyclases","volume":"117","author":"Christianson","year":"2017","journal-title":"Chem. Rev."},{"key":"2026092211025750100_cit2","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1007\/s11094-024-03050-z","article-title":"Sclareol: Isolation, Structural Modification, Biosynthesis,\nand Pharmacological Evaluation \u2013 A Review","volume":"57","author":"Jameel","year":"2024","journal-title":"Pharm. Chem. J."},{"key":"2026092211025750100_cit3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0248954","article-title":"Study of the\ngenetic and phenotypic variation among wild and cultivated clary sages\nprovides interesting avenues for breeding programs of a perfume, medicinal\nand aromatic plant","volume":"16","author":"Chalvin","year":"2021","journal-title":"PLoS One"},{"key":"2026092211025750100_cit4","doi-asserted-by":"publisher","DOI":"10.1038\/s41438-021-00640-w","article-title":"Sclareol and linalyl acetate are produced by glandular\ntrichomes through the MEP pathway","volume":"8","author":"Chalvin","year":"2021","journal-title":"Hortic. Res."},{"key":"2026092211025750100_cit5","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1014105","article-title":"The bioactivities of\nsclareol: A mini review","volume":"13","author":"Zhou","year":"2022","journal-title":"Front. Pharmacol."},{"key":"2026092211025750100_cit6","doi-asserted-by":"publisher","first-page":"18900","DOI":"10.1021\/ja307404u","article-title":"Toward a biosynthetic\nroute to sclareol and amber odorants","volume":"134","author":"Schalk","year":"2012","journal-title":"J. Am.\nChem. Soc."},{"key":"2026092211025750100_cit7","doi-asserted-by":"publisher","first-page":"5042","DOI":"10.1021\/acs.jafc.2c09010","article-title":"From Ambergris\nto (\u2212)-Ambrox: Chemistry Meets\nBiocatalysis for Sustainable (\u2212)-Ambrox Production","volume":"71","author":"Eichhorn","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"2026092211025750100_cit8","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1111\/j.1438-8677.2008.00053.x","article-title":"Diversity\nof essential oil glands of clary sage (Salvia sclarea L., Lamiaceae)","volume":"10","author":"Schmiderer","year":"2008","journal-title":"Plant Biol."},{"key":"2026092211025750100_cit9","first-page":"1","article-title":"Essential\noil composition, antioxidant and antifungal activities of Salvia sclarea L. from Munzur Valley in Tunceli,\nTurkey","volume":"60","author":"Yuce","year":"2014","journal-title":"Cell Mol. Biol."},{"key":"2026092211025750100_cit10","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.jksus.2015.11.001","article-title":"Inhibition of inducible\nnitric oxide synthase gene expression (iNOS) and cytotoxic activity\nof Salvia sclarea L. essential oil","volume":"28","author":"Durgha","year":"2016","journal-title":"J. King Saud Univ., Sci."},{"key":"2026092211025750100_cit11","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s10495-006-0026-8","article-title":"Sclareol induces\napoptosis in human HCT116 colon cancer cells in vitro and suppression\nof HCT116 tumor growth in immunodeficient mice","volume":"12","author":"Dimas","year":"2007","journal-title":"Apoptosis"},{"key":"2026092211025750100_cit12","doi-asserted-by":"publisher","first-page":"S270","DOI":"10.1016\/j.fct.2008.06.074","article-title":"Fragrance material\nreview on sclareol","volume":"46","author":"Bhatia","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"2026092211025750100_cit13","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1094\/MPMI-10-14-0320-R","article-title":"Sclareol induces plant\nresistance to root-knot nematode partially through ethylene-dependent\nenhancement of lignin accumulation","volume":"28","author":"Fujimoto","year":"2015","journal-title":"Mol. Plant\nMicrobe Interact."},{"key":"2026092211025750100_cit14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ymben.2022.11.002","article-title":"Engineering yeast\nfor high-level\nproduction of diterpenoid sclareol","volume":"75","author":"Cao","year":"2023","journal-title":"Metab. Eng."},{"key":"2026092211025750100_cit15","doi-asserted-by":"publisher","first-page":"11753","DOI":"10.1021\/acs.chemrev.6b00834","article-title":"Navigating the Chiral\nPool in the Total Synthesis of Complex Terpene Natural Products","volume":"117","author":"Brill","year":"2017","journal-title":"Chem. Rev."},{"key":"2026092211025750100_cit16","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1021\/acscentsci.3c01518","article-title":"Natural\nProduct Synthesis in the 21st Century: Beyond the Mountain Top","volume":"10","author":"Shenvi","year":"2024","journal-title":"ACS Cent. Sci."},{"key":"2026092211025750100_cit17","doi-asserted-by":"publisher","first-page":"5202","DOI":"10.1039\/D3GC04949C","article-title":"Constructing a green\noleaginous yeast cell factory for sustainable\nproduction of the plant-derived diterpenoid sclareol","volume":"26","author":"Sun","year":"2024","journal-title":"Green Chem."},{"key":"2026092211025750100_cit18","doi-asserted-by":"publisher","DOI":"10.1002\/biot.70285","article-title":"Synthetic Biology of Sclareol: From the Plant Biosynthetic\nPathway to Engineered Microbial and Photosynthetic Chassis","volume":"21","author":"Li","year":"2026","journal-title":"Biotechnol. J."},{"key":"2026092211025750100_cit19","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-025-02699-2","article-title":"Advances in the sustainable\nbiosynthesis\nof valuable terpenoid flavor compounds and precursors in micro-organisms","volume":"18","author":"Li","year":"2025","journal-title":"Biotechnol. Biofuels Bioprod."},{"key":"2026092211025750100_cit20","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2025.1713206","article-title":"Cis-abienol from tobacco trichomes to ambergris-like\ncompounds: advances in biosynthesis, fermentation, and industrial\napplications","volume":"13","author":"Wang","year":"2025","journal-title":"Front. Bioeng. Biotechnol."},{"key":"2026092211025750100_cit21","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1021\/cbe.3c00083","article-title":"Efforts toward\nAmbergris Biosynthesis","volume":"1","author":"He","year":"2024","journal-title":"Chem. Bio Eng."},{"key":"2026092211025750100_cit22","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/10_2015_308","article-title":"Enzymes for synthetic\nbiology of ambroxide-related\nditerpenoid fragrance compounds","volume":"148","author":"Zerbe","year":"2015","journal-title":"Adv. Biochem.\nEng. Biotechnol."},{"key":"2026092211025750100_cit23","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202300309","article-title":"The Scent\nof Change: Sustainable Fragrances Through Industrial Biotechnology","volume":"24","author":"Michailidou","year":"2023","journal-title":"ChemBioChem"},{"key":"2026092211025750100_cit24","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.supflu.2016.12.001","article-title":"Purification\nof sclareol by supercritical CO2 fractionation process","volume":"122","author":"Dufour","year":"2017","journal-title":"J. Supercrit. Fluids"},{"key":"2026092211025750100_cit25","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28093903","article-title":"Supercritical\nFluid Extraction of Essential Oil and Sclareol from a Clary Sage Concrete","volume":"28","author":"Zanotti","year":"2023","journal-title":"Molecules"},{"key":"2026092211025750100_cit26","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216449","article-title":"Combination of Analytical\nand Statistical Methods in Order to Optimize Antibacterial Activity\nof Clary Sage Supercritical Fluid Extracts","volume":"26","author":"Bako\u0301","year":"2021","journal-title":"Molecules"},{"key":"2026092211025750100_cit27","doi-asserted-by":"publisher","DOI":"10.1016\/j.supflu.2020.104754","article-title":"Sclareol purification\nusing the supercritical fractionation process: A modeling case study","volume":"159","author":"Dufour","year":"2020","journal-title":"J. Supercrit. Fluids"},{"key":"2026092211025750100_cit28","doi-asserted-by":"publisher","DOI":"10.3390\/agronomy10081114","article-title":"Agronomic\nEvaluation and Chemical Characterization\nof Sicilian Salvia sclarea L. Accessions","volume":"10","author":"Tuttolomondo","year":"2020","journal-title":"Agronomy"},{"key":"2026092211025750100_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jarmap.2024.100579","article-title":"Multi-environment evaluation\nof Clary sage (Salvia sclarea L.) selections\nfor yield and essential oil traits under Western Himalayan conditions","volume":"43","author":"Kumar","year":"2024","journal-title":"J. Appl. Res. Med. Aromat. Plants"},{"key":"2026092211025750100_cit30","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1111\/nph.14178","article-title":"Why do plants produce so many terpenoid\ncompounds?","volume":"220","author":"Pichersky","year":"2018","journal-title":"New Phytol."},{"key":"2026092211025750100_cit31","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-019-0246-3","article-title":"Stress and\ndefense responses in plant secondary metabolites production","volume":"52","author":"Isah","year":"2019","journal-title":"Biol. Res."},{"key":"2026092211025750100_cit32","doi-asserted-by":"publisher","DOI":"10.1038\/srep32650","article-title":"One-pot synthesis of (\u2212)-Ambrox","volume":"6","author":"Yang","year":"2016","journal-title":"Sci.\nRep."},{"key":"2026092211025750100_cit33","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.01115","article-title":"Stereoselective chemo-enzymatic oxidation routes for\n(1R,3E,7E,11S,12S)-3,7,18-dolabellatriene","volume":"6","author":"Go\u0308rner","year":"2015","journal-title":"Front.\nMicrobiol."},{"key":"2026092211025750100_cit34","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-025-02744-7","article-title":"Combinatorial metabolic\nengineering of Yarrowia lipolytica for high-level production of the\nplant-derived diterpenoid sclareol","volume":"24","author":"Chen","year":"2025","journal-title":"Microb.\nCell Fact."},{"key":"2026092211025750100_cit35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2515324122","article-title":"Engineering chronological\nlifespan toward a robust yeast cell factory","volume":"122","author":"Wu","year":"2025","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026092211025750100_cit36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048253","article-title":"Extracellular\nlocalization of the diterpene sclareol in clary sage (Salvia sclarea L., Lamiaceae)","volume":"7","author":"Caissard","year":"2012","journal-title":"PLoS One"},{"key":"2026092211025750100_cit37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2229-12-119","article-title":"Discovery and functional\ncharacterization of two diterpene synthases for sclareol biosynthesis\nin Salvia sclarea (L.) and their relevance\nfor perfume manufacture","volume":"12","author":"Caniard","year":"2012","journal-title":"BMC Plant Biol."},{"key":"2026092211025750100_cit38","doi-asserted-by":"publisher","first-page":"10427","DOI":"10.1039\/D5CS00760G","article-title":"Radical retrosynthesis:\na powerful\nstrategy for modern assembly of terpenoid natural products","volume":"54","author":"Zhang","year":"2025","journal-title":"Chem. Soc. Rev."},{"key":"2026092211025750100_cit39","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/s41557-020-0439-y","article-title":"Total synthesis of terpenes via palladium-catalysed cyclization strategy","volume":"12","author":"Trost","year":"2020","journal-title":"Nat. Chem."},{"key":"2026092211025750100_cit40","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s42994-021-00050-5","article-title":"Plant geranylgeranyl\ndiphosphate synthases: every (gene)\nfamily has a story","volume":"2","author":"Barja","year":"2021","journal-title":"aBIOTECH"},{"key":"2026092211025750100_cit41","doi-asserted-by":"publisher","DOI":"10.1016\/j.engmic.2022.100058","article-title":"Sustainable\nbiosynthesis of valuable\nditerpenes in microbes","volume":"3","author":"Liu","year":"2023","journal-title":"Eng. Microbiol."},{"key":"2026092211025750100_cit42","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.phytochem.2018.12.003","article-title":"Cytochrome P450 enzymes:\nA driving force of plant diterpene\ndiversity","volume":"161","author":"Bathe","year":"2019","journal-title":"Phytochemistry"},{"key":"2026092211025750100_cit43","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.copbio.2014.12.004","article-title":"Production of natural\nproducts through metabolic engineering\nof Saccharomyces cerevisiae","volume":"35","author":"Krivoruchko","year":"2015","journal-title":"Curr. Opin. Biotechnol."},{"key":"2026092211025750100_cit44","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1039\/D3NP00005B","article-title":"Engineering yeast for\nthe production of plant terpenoids using synthetic biology approaches","volume":"40","author":"Bureau","year":"2023","journal-title":"Nat. Prod. Rep."},{"key":"2026092211025750100_cit45","doi-asserted-by":"publisher","DOI":"10.1016\/j.mec.2022.e00213","article-title":"Engineering of Yarrowia lipolytica for terpenoid production","volume":"15","author":"Arnesen","year":"2022","journal-title":"Metab. Eng. Commun."},{"key":"2026092211025750100_cit46","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1021\/acssynbio.5c00834","article-title":"Enhanced Biosynthesis\nof Sclareol in Yarrowia lipolytica\nvia Systematic Metabolic Engineering","volume":"15","author":"Huang","year":"2026","journal-title":"ACS Synth.\nBiol."},{"key":"2026092211025750100_cit47","unstructured":"Mengyao, Z.; Fan, B.; Yiwei, S.; Peng, C.; Yongjin, J. Z.\n          Expanding the versatility of the protein master Pichia\npastoris towards efficient biosynthesis of diterpenoid sclareol\n          Trends Biotechnol.\n          2026\n          10.1016\/j.tibtech.2026.04.026."},{"key":"2026092211025750100_cit48","doi-asserted-by":"publisher","first-page":"667","DOI":"10.4014\/jmb.1904.04015","article-title":"Synthetic Biology Tools for Novel Secondary Metabolite\nDiscovery in Streptomyces","volume":"29","author":"Lee","year":"2019","journal-title":"J. Microbiol. Biotechnol."},{"key":"2026092211025750100_cit49","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.tibtech.2019.01.003","article-title":"Systems Metabolic\nEngineering Strategies: Integrating\nSystems and Synthetic Biology with Metabolic Engineering","volume":"37","author":"Choi","year":"2019","journal-title":"Trends Biotechnol."},{"key":"2026092211025750100_cit50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56278-y","article-title":"Engineered CRISPR-Cas9\nfor Streptomyces\nsp. genome editing to improve specialized metabolite production","volume":"16","author":"Kim","year":"2025","journal-title":"Nat. Commun."},{"key":"2026092211025750100_cit51","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2019.112082","article-title":"Heterologous\nproduction of labdane-type\nditerpenes in the green alga Chlamydomonas reinhardtii","volume":"167","author":"Papaefthimiou","year":"2019","journal-title":"Phytochemistry"},{"key":"2026092211025750100_cit52","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ymben.2022.06.002","article-title":"Engineering a powerful\ngreen cell factory for robust photoautotrophic\nditerpenoid production","volume":"73","author":"Einhaus","year":"2022","journal-title":"Metab. Eng."},{"key":"2026092211025750100_cit53","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1021\/acssynbio.0c00632","article-title":"Rational Promoter Engineering Enables\nRobust Terpene Production in\nMicroalgae","volume":"10","author":"Einhaus","year":"2021","journal-title":"ACS Synth. Biol."},{"key":"2026092211025750100_cit54","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2022.937095","article-title":"Hairy roots:\nAn untapped potential for production of\nplant products","volume":"13","author":"Morey","year":"2022","journal-title":"Front. Plant Sci."},{"key":"2026092211025750100_cit55","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.tibtech.2020.06.012","article-title":"Biotechnological\nExploration of Transformed Root Culture for Value-Added Products","volume":"39","author":"Shi","year":"2021","journal-title":"Trends Biotechnol."},{"key":"2026092211025750100_cit56","doi-asserted-by":"publisher","first-page":"13812","DOI":"10.1021\/acs.jafc.4c02442","article-title":"Engineering Sclareol\nProduction on the Leaf Surface of Nicotiana tabacum","volume":"72","author":"Ma","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"2026092211025750100_cit57","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1042\/EBC20160024","article-title":"Construction\nof\na minimal genome as a chassis for synthetic biology","volume":"60","author":"Sung","year":"2016","journal-title":"Essays Biochem."},{"key":"2026092211025750100_cit58","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.594061","article-title":"Current Challenges and Opportunities\nin Non-native Chemical Production by Engineered Yeasts","volume":"8","author":"Kim","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"2026092211025750100_cit59","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-022-01819-z","article-title":"Compartmentalization and transporter engineering strategies\nfor terpenoid\nsynthesis","volume":"21","author":"Jin","year":"2022","journal-title":"Microb. Cell Fact."},{"key":"2026092211025750100_cit60","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2426686122","article-title":"High-throughput metabolic engineering\nof Yarrowia lipolytica through gene expression tuning","volume":"122","author":"Jiang","year":"2025","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026092211025750100_cit61","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1016\/S0021-9258(19)83726-2","article-title":"Biosynthesis\nof sclareol, beta-sitosterol, and oleanolic acid from mevalonic acid-2-C-14","volume":"237","author":"Nicholas","year":"1962","journal-title":"J. Biol. Chem."},{"key":"2026092211025750100_cit62","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1039\/C3NP70124G","article-title":"Methylerythritol 4-phosphate (MEP)\npathway metabolic\nregulation","volume":"31","author":"Banerjee","year":"2014","journal-title":"Nat. Prod. Rep."},{"key":"2026092211025750100_cit63","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/nbt.2149","article-title":"Design of a dynamic sensor-regulator\nsystem for production of chemicals and fuels derived from fatty acids","volume":"30","author":"Zhang","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"2026092211025750100_cit64","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1039\/C9NP00016J","article-title":"Recent advances of metabolic engineering\nstrategies in natural isoprenoid production using cell factories","volume":"37","author":"Li","year":"2020","journal-title":"Nat. Prod. Rep."},{"key":"2026092211025750100_cit65","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1016\/j.cell.2016.02.004","article-title":"Engineering Cellular Metabolism","volume":"164","author":"Nielsen","year":"2016","journal-title":"Cell"},{"key":"2026092211025750100_cit66","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1021\/acssuschemeng.2c06716","article-title":"Construction of\nan Artificial Microbial Consortium for Green Production of (\u2212)-Ambroxide","volume":"11","author":"He","year":"2023","journal-title":"ACS Sustainable Chem. Eng."},{"key":"2026092211025750100_cit67","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/nbt.1557","article-title":"Synthetic protein\nscaffolds provide modular control over metabolic flux","volume":"27","author":"Dueber","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"2026092211025750100_cit68","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1038\/nbt.3018","article-title":"Enzyme clustering\naccelerates processing of intermediates through metabolic channeling","volume":"32","author":"Castellana","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"2026092211025750100_cit69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007084","article-title":"Machine and deep learning\nmeet genome-scale metabolic modeling","volume":"15","author":"Zampieri","year":"2019","journal-title":"PLoS Comput.\nBiol."},{"key":"2026092211025750100_cit70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.copbio.2019.08.010","article-title":"Machine learning\napplications in systems metabolic engineering","volume":"64","author":"Kim","year":"2020","journal-title":"Curr. Opin. Biotechnol."},{"key":"2026092211025750100_cit71","doi-asserted-by":"publisher","first-page":"4143","DOI":"10.1002\/anie.201708408","article-title":"Directed\nEvolution: Bringing New Chemistry to Life","volume":"57","author":"Arnold","year":"2018","journal-title":"Angew.\nChem., Int. Ed."},{"key":"2026092211025750100_cit72","doi-asserted-by":"publisher","first-page":"3351","DOI":"10.1002\/anie.201409470","article-title":"Expanding the enzyme universe: accessing\nnon-natural reactions by mechanism-guided directed evolution","volume":"54","author":"Renata","year":"2015","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026092211025750100_cit73","doi-asserted-by":"publisher","DOI":"10.1016\/j.indcrop.2026.122810","article-title":"Dual gene engineering of SsdTPS and SsSCS boosted secondary\nmetabolites synthesis and drought tolerance via activation of metabolic\nand stress signaling pathways","volume":"241","author":"Yao","year":"2026","journal-title":"Ind. Crops Prod."},{"key":"2026092211025750100_cit74","doi-asserted-by":"publisher","first-page":"15368","DOI":"10.1021\/jacs.6b07394","article-title":"Harnessing\nYeast Peroxisomes for\nBiosynthesis of Fatty-Acid-Derived Biofuels and Chemicals with Relieved\nSide-Pathway Competition","volume":"138","author":"Zhou","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"2026092211025750100_cit75","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nature19769","article-title":"Rewriting yeast\ncentral carbon metabolism for industrial isoprenoid production","volume":"537","author":"Meadows","year":"2016","journal-title":"Nature"},{"key":"2026092211025750100_cit76","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1146\/annurev.arplant.043008.091955","article-title":"Biosynthesis of plant isoprenoids: perspectives for\nmicrobial engineering","volume":"60","author":"Kirby","year":"2009","journal-title":"Annu. Rev. Plant Biol."},{"key":"2026092211025750100_cit77","doi-asserted-by":"publisher","DOI":"10.1093\/jimb\/kuab050","article-title":"Engineering acetyl-CoA\nsupply and ERG9 repression to\nenhance mevalonate production in Saccharomyces cerevisiae","volume":"48","author":"Wegner","year":"2021","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"2026092211025750100_cit78","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.ymben.2014.10.008","article-title":"Efficient\nditerpene production in yeast by engineering Erg20p into a geranylgeranyl\ndiphosphate synthase","volume":"27","author":"Ignea","year":"2015","journal-title":"Metab. Eng."},{"key":"2026092211025750100_cit79","doi-asserted-by":"publisher","first-page":"9246","DOI":"10.1021\/acs.jafc.2c03917","article-title":"Advances in Metabolic\nEngineering Paving the Way for the Efficient Biosynthesis of Terpenes\nin Yeasts","volume":"70","author":"Li","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"2026092211025750100_cit80","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15005-4","article-title":"Engineering Saccharomyces\ncerevisiae\nfor geranylgeraniol overproduction by combinatorial design","volume":"7","author":"Song","year":"2017","journal-title":"Sci. Rep."},{"key":"2026092211025750100_cit81","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3595","article-title":"Programming adaptive\ncontrol to evolve increased metabolite\nproduction","volume":"4","author":"Chou","year":"2013","journal-title":"Nat. Commun."},{"key":"2026092211025750100_cit82","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48452-2","article-title":"An automated\npipeline for the screening of diverse monoterpene synthase libraries","volume":"9","author":"Leferink","year":"2019","journal-title":"Sci. Rep."},{"key":"2026092211025750100_cit83","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10008","article-title":"Ultrahigh-throughput\ndiscovery of promiscuous enzymes\nby picodroplet functional metagenomics","volume":"6","author":"Colin","year":"2015","journal-title":"Nat.\nCommun."},{"key":"2026092211025750100_cit84","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ymben.2020.10.005","article-title":"Machine learning\nfor metabolic engineering: A review","volume":"63","author":"Lawson","year":"2021","journal-title":"Metab.\nEng."},{"key":"2026092211025750100_cit85","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.1016\/j.csbj.2023.03.045","article-title":"Machine learning for metabolic pathway optimization:\nA review","volume":"21","author":"Cheng","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"2026092211025750100_cit86","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408705","article-title":"Multi-Omics,\nMachine Learning-Aware,\nGenome-Wide Metabolic Model of Bacillus Subtilis Refines the Gene\nExpression and Cell Growth Prediction","volume":"11","author":"Bi","year":"2024","journal-title":"Adv.\nSci."},{"key":"2026092211025750100_cit87","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-018-1285-7","article-title":"Synthesis and techno-economic assessment\nof microbial-based\nprocesses for terpenes production","volume":"11","author":"Wu","year":"2018","journal-title":"Biotechnol.\nBiofuels"},{"key":"2026092211025750100_cit88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2021.126661","article-title":"Techno-economic\nand profitability analysis of extraction\nof patchouli oil using supercritical carbon dioxide","volume":"297","author":"Soh","year":"2021","journal-title":"J. Cleaner Prod."},{"key":"2026092211025750100_cit89","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2019.122666","article-title":"Techno-economic\nassessment of microbial\nlimonene production","volume":"300","author":"Sun","year":"2020","journal-title":"Bioresour. Technol."},{"key":"2026092211025750100_cit90","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00575","article-title":"Microbial\nelectron transport and\nenergy conservation\u2013the foundation for optimizing bioelectrochemical\nsystems","volume":"6","author":"Kracke","year":"2015","journal-title":"Front. Microbiol."},{"key":"2026092211025750100_cit91","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/nrmicro.2016.130","article-title":"Harnessing the power of microbial autotrophy","volume":"14","author":"Claassens","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"2026092211025750100_cit92","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2022.127906","article-title":"Microbial electrosynthesis from carbon\ndioxide feedstock\nlinked to yeast growth for the production of high-value isoprenoids","volume":"363","author":"Yadav","year":"2022","journal-title":"Bioresour. Technol."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c07601","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/37\/54870\/68401166\/acsomega.6c07601.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/37\/54870\/68401166\/acsomega.6c07601.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:44:22Z","timestamp":1790091862000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/37\/54870\/5422227\/Sclareol-Production-Driven-by-Advanced-Synthetic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":92,"journal-issue":{"issue":"37","published-online":{"date-parts":[[2026,9,7]]},"published-print":{"date-parts":[[2026,9,22]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c07601","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}