{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:13:01Z","timestamp":1788221581461,"version":"build-2803163510"},"reference-count":76,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004192","name":"National Science and Technology Development Agency","doi-asserted-by":"publisher","award":["B16F640052"],"award-info":[{"award-number":["B16F640052"]}],"id":[{"id":"10.13039\/501100004192","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016204","name":"Ministry of Higher Education, Science, Research and Innovation, Thailand","doi-asserted-by":"publisher","award":["P-18-52488"],"award-info":[{"award-number":["P-18-52488"]}],"id":[{"id":"10.13039\/501100016204","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"publisher","award":["FFB690024-0337"],"award-info":[{"award-number":["FFB690024-0337"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Optimization of microbial production by synthetic biology is essential for industrial and sustainable biotechnology applications. \u03b2-carotene is a high-value compound that can be heterologously produced in the budding yeast Saccharomyces cerevisiae, providing an alternative to natural extraction. In this study, we aimed to enhance \u03b2-carotene production by machine learning\u2013guided combinatorial strain engineering and transcriptomic analyses. We fine-tuned the expression of rate-limiting enzymes in the mevalonate (MVA) pathway through combinatorial engineering of promoters and terminators. XGBoost was applied to the Design-Build-Test-Learn (DBTL) cycle to facilitate rapid optimization. In the second DBTL cycle of 1 mL culture screening, fine-tuning MVA gene expression resulted in a 139% improvement in \u03b2-carotene titer. Additionally, guided by transcriptomic insights into altered expression of iron uptake genes, we supplemented \u03b2-carotene production cultures with iron, resulting in a 70.54% increase in \u03b2-carotene titer. Furthermore, integrating the fine-tuned MVA cassette with iron supplementation in 250 mL shake-flasks yielded up to 72.07 mg\/L of \u03b2-carotene at 72 h, representing a 67.79% increase compared to the \u03b2-carotene-producing strain without MVA gene fine-tuning. Our study demonstrates the effectiveness of XGBoost in predicting complex combinatorial designs and highlights the potential of combining machine learning and transcriptomic insights to optimize non-native biochemical production in yeast.<\/jats:p>","DOI":"10.1021\/acsomega.6c06012","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T21:02:24Z","timestamp":1786482144000},"page":"50249-50263","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Machine\nLearning and Transcriptomics to\nEnhance \u03b2-Carotene Production in\n                    <i>Saccharomyces cerevisiae<\/i>"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4814-6308","authenticated-orcid":true,"given":"Peerapat","family":"Khamwachirapithak","sequence":"first","affiliation":[{"name":"Thammasat University , , Phahonyothin Road, Khlong Luang , , ,","place":["Bangkok, Pathum Thani, Thailand, 12120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittapong","family":"Sae-Tang","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang , , ,","place":["Bangkok, Pathum Thani, Thailand, 12120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suriyaporn","family":"Bubphasawan","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang , , ,","place":["Bangkok, Pathum Thani, Thailand, 12120"]},{"name":"National Science and Technology Development Agency (NSTDA) , , 333 EECi Headquarters Wang Chan , ,","place":["Rayong, Thailand, 21210"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongrak","family":"Choompuper","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang , , ,","place":["Bangkok, Pathum Thani, Thailand, 12120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-6571","authenticated-orcid":true,"given":"Xin-Qing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University , , ,","place":["Shanghai, People\u2019s Republic of China, 200240"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-1340","authenticated-orcid":true,"given":"Verawat","family":"Champreda","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang , , ,","place":["Bangkok, Pathum Thani, Thailand, 12120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5707-3516","authenticated-orcid":true,"given":"Weerawat","family":"Runguphan","sequence":"additional","affiliation":[{"name":"National Science and Technology Development Agency (NSTDA) , , 111 Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang , , ,","place":["Bangkok, Pathum Thani, Thailand, 12120"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"2026083119130182200_cit1","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1111\/1574-6976.12073","article-title":"Improving industrial yeast strains: exploiting natural\nand artificial diversity","volume":"38","author":"Steensels","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"2026083119130182200_cit2","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1021\/ef502349v","article-title":"Substrate\nand Product Inhibition on Yeast Performance in Ethanol Fermentation","volume":"29","author":"Zhang","year":"2015","journal-title":"Energy Fuels"},{"key":"2026083119130182200_cit3","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1111\/j.1567-1364.2008.00428.x","article-title":"Yeast selection\nfor fuel ethanol production in Brazil","volume":"8","author":"Basso","year":"2008","journal-title":"FEMS\nYeast Res."},{"key":"2026083119130182200_cit4","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.biotechadv.2011.09.011","article-title":"Production of recombinant proteins by yeast cells","volume":"30","author":"C\u0327elik","year":"2012","journal-title":"Biotechnol. Adv."},{"key":"2026083119130182200_cit5","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1263\/jbb.101.172","article-title":"d-Lactic acid\nproduction by metabolically engineered Saccharomyces cerevisiae","volume":"101","author":"Ishida","year":"2006","journal-title":"J. Biosci. Bioeng."},{"key":"2026083119130182200_cit6","doi-asserted-by":"publisher","first-page":"4342","DOI":"10.1128\/AEM.02759-06","article-title":"High-Level Production of Beta-Carotene\nin Saccharomyces cerevisiaeby Successive Transformation\nwith Carotenogenic Genes from Xanthophyllomyces dendrorhous","volume":"73","author":"Verwaal","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"2026083119130182200_cit7","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-018-1227-4","article-title":"Astaxanthin overproduction\nin yeast by strain engineering and new gene target uncovering","volume":"11","author":"Jin","year":"2018","journal-title":"Biotechnol. Biofuels"},{"key":"2026083119130182200_cit8","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/foab062","article-title":"Novel carotenogenic gene combinations\nfrom red yeasts enhanced lycopene and beta-carotene production in\nSaccharomyces cerevisiae from the low-cost substrate sucrose","volume":"21","author":"Watcharawipas","year":"2021","journal-title":"FEMS Yeast Res."},{"key":"2026083119130182200_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.envadv.2023.100440","article-title":"Principles\nof green microbiology: The microbial blueprint for sustainable development","volume":"14","author":"Akinsemolu","year":"2023","journal-title":"Environ. Adv."},{"key":"2026083119130182200_cit10","doi-asserted-by":"publisher","DOI":"10.71150\/jm.2501022","article-title":"Synthetic biology\nstrategies for sustainable Bioplastic\nproduction by yeasts","volume":"63","author":"Le","year":"2025","journal-title":"J. Microbiol."},{"key":"2026083119130182200_cit11","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1111\/jpn.13375","article-title":"Health benefits of\ncarotenoids and potential application\nin poultry industry: A review","volume":"104","author":"Nabi","year":"2020","journal-title":"J. Anim. Physiol.\nAnim. Nutr."},{"key":"2026083119130182200_cit12","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.abb.2018.06.001","article-title":"Carotenoids\nin human nutrition and health","volume":"652","author":"Eggersdorfer","year":"2018","journal-title":"Arch. Biochem.\nBiophys."},{"key":"2026083119130182200_cit13","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/foaa068","article-title":"Metabolic\nengineering of Saccharomyces cerevisiae for production of \u03b2-carotene\nfrom hydrophobic substrates","volume":"21","author":"Fathi","year":"2021","journal-title":"FEMS Yeast Res."},{"key":"2026083119130182200_cit14","doi-asserted-by":"publisher","DOI":"10.1093\/jimb\/kuad009","article-title":"Enhanced \u03b2-carotene\nproduction in Yarrowia lipolytica through the metabolic and fermentation\nengineering","volume":"50","author":"Jing","year":"2023","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"2026083119130182200_cit15","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1007\/s12010-018-2787-2","article-title":"Enhanced\nProduction of Crude Violacein from Glucose in Escherichia coli by Overexpression of Rate-Limiting Key Enzyme(S)\nInvolved in Violacein Biosynthesis","volume":"186","author":"Zhou","year":"2018","journal-title":"Appl. Biochem.\nBiotechnol."},{"key":"2026083119130182200_cit16","doi-asserted-by":"publisher","first-page":"11148","DOI":"10.1021\/acs.jafc.9b04519","article-title":"Systematic Metabolic\nEngineering of Saccharomyces cerevisiae for Lycopene Overproduction","volume":"67","author":"Shi","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"2026083119130182200_cit17","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00284-011-0044-9","article-title":"Enhancement of \u03b2-carotene\nproduction\nby over-expression of HMG-CoA reductase coupled with addition of ergosterol\nbiosynthesis inhibitors in recombinant Saccharomyces cerevisiae","volume":"64","author":"Yan","year":"2012","journal-title":"Curr. Microbiol."},{"key":"2026083119130182200_cit18","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1038\/nprot.2014.132","article-title":"Production\nand quantification\nof sesquiterpenes in Saccharomyces cerevisiae, including extraction,\ndetection and quantification of terpene products and key related metabolites","volume":"9","author":"Rodriguez","year":"2014","journal-title":"Nat. Protoc."},{"key":"2026083119130182200_cit19","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ymben.2013.11.002","article-title":"Improving carotenoids production\nin yeast via adaptive laboratory evolution","volume":"21","author":"Reyes","year":"2014","journal-title":"Metab. Eng."},{"key":"2026083119130182200_cit20","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.jbiotec.2009.01.008","article-title":"Combinatorial\nexpression of bacterial whole mevalonate pathway for the production\nof beta-carotene in E. coli","volume":"140","author":"Yoon","year":"2009","journal-title":"J. Biotechnol."},{"key":"2026083119130182200_cit21","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1002\/bit.21766","article-title":"Redirection\nof flux\nthrough the FPP branch-point in Saccharomyces cerevisiae by down-regulating\nsqualene synthase","volume":"100","author":"Paradise","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"2026083119130182200_cit22","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202300285","article-title":"Building a machine-learning model\nto predict optimal mevalonate pathway\ngene expression levels for efficient production of a carotenoid in\nyeast","volume":"19","author":"Shimazaki","year":"2024","journal-title":"Biotechnol. J."},{"key":"2026083119130182200_cit23","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ymben.2022.10.004","article-title":"Machine-learning guided elucidation\nof contribution of individual steps in the mevalonate pathway and\nconstruction of a yeast platform strain for terpenoid production","volume":"74","author":"Mukherjee","year":"2022","journal-title":"Metab. Eng."},{"key":"2026083119130182200_cit24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18008-4","article-title":"A machine\nlearning Automated Recommendation Tool for synthetic biology","volume":"11","author":"Radivojevic\u0301","year":"2020","journal-title":"Nat. Commun."},{"key":"2026083119130182200_cit25","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1021\/acssynbio.3c00199","article-title":"Optimizing Ethanol Production in\nSaccharomyces cerevisiae\nat Ambient and Elevated Temperatures through Machine Learning-Guided\nCombinatorial Promoter Modifications","volume":"12","author":"Khamwachirapithak","year":"2023","journal-title":"ACS Synth.\nBiol."},{"key":"2026083119130182200_cit26","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-022-03515-x","article-title":"Construction of a machine-learning\nmodel to predict the optimal gene expression level for efficient production\nof d-lactic acid in yeast","volume":"39","author":"Yamamoto","year":"2023","journal-title":"World J. Microbiol.\nBiotechnol."},{"key":"2026083119130182200_cit27","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.ymben.2018.03.020","article-title":"MiYA, an efficient\nmachine-learning workflow in conjunction with the YeastFab assembly\nstrategy for combinatorial optimization of heterologous metabolic\npathways in Saccharomyces cerevisiae","volume":"47","author":"Zhou","year":"2018","journal-title":"Metab.\nEng."},{"key":"2026083119130182200_cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2022.128455","article-title":"Machine learning-guided prediction\nof potential engineering targets for microbial production of lycopene","volume":"369","author":"Kang","year":"2023","journal-title":"Bioresour. Technol."},{"key":"2026083119130182200_cit29","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1021\/acssynbio.8b00398","article-title":"Machine\nLearning of Designed Translational Control Allows Predictive Pathway\nOptimization in Escherichia coli","volume":"8","author":"Jervis","year":"2019","journal-title":"ACS Synth. Biol."},{"key":"2026083119130182200_cit30","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.6.e23","article-title":"A second\nset of loxP marker cassettes for Cre-mediated multiple gene knockouts\nin budding yeast","volume":"30","author":"Gueldener","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2026083119130182200_cit31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nprot.2007.17","article-title":"Frozen competent yeast cells that\ncan be transformed\nwith high efficiency using the LiAc\/SS carrier DNA\/PEG method","volume":"2","author":"Gietz","year":"2007","journal-title":"Nat. Protoc."},{"key":"2026083119130182200_cit32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.168355","article-title":"Characterizing Different Modes of\nInterplay Between Rap1 and H3 Using Inducible H3-depletion Yeast","volume":"435","author":"Khamwachirapithak","year":"2023","journal-title":"J. Mol. Biol."},{"key":"2026083119130182200_cit33","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based\ngenome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"2026083119130182200_cit34","unstructured":"Institute, B.\n          . Picard ToolkitGithub respository2019."},{"key":"2026083119130182200_cit35","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"StringTie enables\nimproved reconstruction of a transcriptome\nfrom RNA-seq reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"2026083119130182200_cit36","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated\nestimation of fold change\nand dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2026083119130182200_cit37","unstructured":"Team, R. C.\n          . R: A language and environment\nfor statistical computing. 2021."},{"key":"2026083119130182200_cit38","doi-asserted-by":"publisher","first-page":"3710","DOI":"10.1093\/bioinformatics\/bth456","article-title":"GO:TermFinder--open\nsource software\nfor accessing Gene Ontology information and finding significantly\nenriched Gene Ontology terms associated with a list of genes","volume":"20","author":"Boyle","year":"2004","journal-title":"Bioinformatics"},{"key":"2026083119130182200_cit39","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyae185","article-title":"Saccharomyces\nGenome\nDatabase: Advances in Genome Annotation, Expanded Biochemical Pathways,\nand Other Key Enhancements","volume":"229","author":"Engel","year":"2024","journal-title":"Genetics."},{"key":"2026083119130182200_cit40","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING\ndatabase in 2023: protein-protein association networks and functional\nenrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"2026083119130182200_cit41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005553","article-title":"Golden Gate\nShuffling: A One-Pot DNA Shuffling Method Based on Type IIs Restriction\nEnzymes","volume":"4","author":"Engler","year":"2009","journal-title":"PLoS One"},{"key":"2026083119130182200_cit42","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv464","article-title":"YeastFab:\nthe design and construction of standard biological\nparts for metabolic engineering in Saccharomyces cerevisiae","volume":"43","author":"Guo","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2026083119130182200_cit43","doi-asserted-by":"publisher","DOI":"10.1186\/s13036-015-0005-0","article-title":"Parallel use\nof shake flask and microtiter plate online measuring devices (RAMOS\nand BioLector) reduces the number of experiments in laboratory-scale\nstirred tank bioreactors","volume":"9","author":"Wewetzer","year":"2015","journal-title":"J. Biol. Eng."},{"key":"2026083119130182200_cit44","doi-asserted-by":"crossref","unstructured":"Chen, T.; Guestrin, C. In  XGBoost:\nA Scalable\nTree Boosting System, Proceedings of the 22nd ACM SIGKDD\nInternational Conference on Knowledge Discovery and Data Mining; Association for Computing Machinery: San Francisco, California, USA, 2016; pp 785\u2013794.","DOI":"10.1145\/2939672.2939785"},{"key":"2026083119130182200_cit45","unstructured":"Chen, T.; He, T.; Benesty, M.; Khotilovich, V.; Tang, Y.; Cho, H.; Chen, K.; Mitchell, R.; Cano, I.; Zhou, T.; Li, M.; Xie, J.; Lin, M.; Geng, Y.; Li, Y.; Yuan, J.\n          xgboost: Extreme Gradient Boosting. 2022."},{"key":"2026083119130182200_cit46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building Predictive\nModels in R Using the caret Package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J. Stat.\nSoftware"},{"key":"2026083119130182200_cit47","doi-asserted-by":"crossref","unstructured":"Wickham H. ggplot2 Elegant Graphics for Data Analysis; Springer International Publishing: Cham, 2016.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"2026083119130182200_cit48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v021.i12","article-title":"Reshaping\nData with the reshape Package","volume":"21","author":"Wickham","year":"2007","journal-title":"J. Stat. Software"},{"key":"2026083119130182200_cit49","unstructured":"Wickham, H.; Henry, L.; Mu\u0308ller, K.; Vaughan, D.\n          dplyr: A\nGrammar of Data\nManipulation, R package version 1.1.4, 2023."},{"key":"2026083119130182200_cit50","unstructured":"Bryan, H. W. a. J.\n          \n          readxl:\nRead Excel Files. 2023."},{"key":"2026083119130182200_cit51","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-017-0728-x","article-title":"Coupling\ngene regulatory patterns to bioprocess conditions to optimize synthetic\nmetabolic modules for improved sesquiterpene production in yeast","volume":"10","author":"Peng","year":"2017","journal-title":"Biotechnol. Biofuels"},{"key":"2026083119130182200_cit52","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41586-019-0978-9","article-title":"Complete biosynthesis of cannabinoids and their unnatural\nanalogues in yeast","volume":"567","author":"Luo","year":"2019","journal-title":"Nature"},{"key":"2026083119130182200_cit53","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-015-0278-5","article-title":"Controlling\nheterologous gene expression inyeast cell factories on different carbon\nsubstrates and across the diauxic shift: acomparison of yeast promoter\nactivities","volume":"14","author":"Peng","year":"2015","journal-title":"Microb. Cell Fact."},{"key":"2026083119130182200_cit54","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ymben.2013.07.001","article-title":"Use of\nexpression-enhancing\nterminators in Saccharomyces cerevisiae to increase mRNA half-life\nand improve gene expression control for metabolic engineering applications","volume":"19","author":"Curran","year":"2013","journal-title":"Metab. Eng."},{"key":"2026083119130182200_cit55","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1021\/acssynbio.1c00117","article-title":"Precise Prediction\nof Promoter Strength Based on a De Novo Synthetic Promoter Library\nCoupled with Machine Learning","volume":"11","author":"Zhao","year":"2022","journal-title":"ACS Synth. Biol."},{"key":"2026083119130182200_cit56","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-017-2215-8","article-title":"Mechanisms of iron sensing and regulation\nin the yeast Saccharomyces cerevisiae","volume":"33","author":"Marti\u0301nez-Pastor","year":"2017","journal-title":"World\nJ. Microbiol. Biotechnol."},{"key":"2026083119130182200_cit57","first-page":"175","article-title":"Stability of Beta-carotene\nunder Different Laboratory Conditions","volume-title":"Methods in Enzymology","author":"Scita","year":"1992"},{"key":"2026083119130182200_cit58","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/B978-0-12-817380-0.00013-0","article-title":"Measuring Chemical Deterioration\nof Foods","volume-title":"Chemical Changes During Processing\nand Storage of Foods","author":"Liu","year":"2021"},{"key":"2026083119130182200_cit59","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ymben.2022.06.001","article-title":"Efficient\nproduction of retinol in Yarrowia lipolytica\nby increasing stability using antioxidant and detergent extraction","volume":"73","author":"Park","year":"2022","journal-title":"Metab. Eng."},{"key":"2026083119130182200_cit60","doi-asserted-by":"publisher","first-page":"18331","DOI":"10.1021\/acsomega.2c00483","article-title":"Transcriptional\nTuning of Mevalonate\nPathway Enzymes to Identify the Impact on Limonene Production in Escherichia coli","volume":"7","author":"Shin","year":"2022","journal-title":"ACS Omega"},{"key":"2026083119130182200_cit61","doi-asserted-by":"publisher","first-page":"10668","DOI":"10.1093\/nar\/gkt809","article-title":"Expression-level\noptimization of a multi-enzyme pathway in the absence of a high-throughput\nassay","volume":"41","author":"Lee","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2026083119130182200_cit62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010177","article-title":"Strain design\noptimization using reinforcement learning","volume":"18","author":"Sabzevari","year":"2022","journal-title":"PLOS\nComput. Biol."},{"key":"2026083119130182200_cit63","doi-asserted-by":"publisher","first-page":"2588","DOI":"10.1021\/acssynbio.3c00186","article-title":"Simulated Design\u2013Build\u2013Test\u2013Learn\nCycles for Consistent Comparison of Machine Learning Methods in Metabolic\nEngineering","volume":"12","author":"van Lent","year":"2023","journal-title":"ACS Synth. Biol."},{"key":"2026083119130182200_cit64","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1021\/acssynbio.4c00035","article-title":"Machine Learning-Guided\nOptimization of p-Coumaric Acid Production in Yeast","volume":"13","author":"Moreno-Paz","year":"2024","journal-title":"ACS Synth. Biol."},{"key":"2026083119130182200_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":"2026083119130182200_cit66","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19092-2","article-title":"The second decade of\nsynthetic biology: 2010\u20132020","volume":"11","author":"Meng","year":"2020","journal-title":"Nat. Commun."},{"key":"2026083119130182200_cit67","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.1021\/acs.jproteome.1c00035","article-title":"Iron Deficiency\nand Recovery in Yeast: A Quantitative\nProteomics Approach","volume":"20","author":"Navarrete-Perea","year":"2021","journal-title":"J. Proteome Res."},{"key":"2026083119130182200_cit68","doi-asserted-by":"publisher","first-page":"14823","DOI":"10.1074\/jbc.M109.091710","article-title":"Metabolic\nResponse to Iron Deficiency in Saccharomyces cerevisiae","volume":"285","author":"Shakoury-Elizeh","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2026083119130182200_cit69","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1128\/jb.57.2.235-246.1949","article-title":"Factors producing high yeast yields in synthetic media","volume":"57","author":"Olson","year":"1949","journal-title":"J. Bacteriol."},{"key":"2026083119130182200_cit70","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1007\/s10534-024-00592-3","article-title":"Production of iron-enriched yeast\nand it\u2019s application\nin the treatment of iron-deficiency anemia","volume":"37","author":"Chen","year":"2024","journal-title":"BioMetals"},{"key":"2026083119130182200_cit71","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1590\/S1517-83822014000200016","article-title":"The uptake of different\niron salts by the yeast Saccharomyces cerevisiae","volume":"45","author":"Gaensly","year":"2014","journal-title":"Braz J. Microbiol."},{"key":"2026083119130182200_cit72","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/foae006","article-title":"Increased production of isobutanol\nfrom xylose through metabolic engineering of Saccharomyces cerevisiae\noverexpressing transcription factor Znf1 and exogenous genes","volume":"24","author":"Songdech","year":"2024","journal-title":"FEMS Yeast Res."},{"key":"2026083119130182200_cit73","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01116","article-title":"Discovery of Several\nNovel Targets that Enhance \u03b2-Carotene\nProduction in Saccharomyces cerevisiae","volume":"8","author":"Li","year":"2017","journal-title":"Front.\nMicrobiol."},{"key":"2026083119130182200_cit74","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00171","article-title":"Build Your\nBioprocess on a Solid\nStrain\u2500\u03b2-Carotene Production in Recombinant Saccharomyces\ncerevisiae","volume":"7","author":"Lo\u0301pez","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"2026083119130182200_cit75","doi-asserted-by":"publisher","first-page":"3522","DOI":"10.1002\/bit.27508","article-title":"High-level \u03b2-carotene\nproduction from xylose by engineered Saccharomyces cerevisiae without\noverexpression of a truncated HMG1 (tHMG1)","volume":"117","author":"Sun","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"2026083119130182200_cit76","doi-asserted-by":"publisher","first-page":"9187","DOI":"10.1021\/acs.jafc.5c00088","article-title":"Construction of Saccharomyces cerevisiae Platform Strain for the\nBiosynthesis of Carotenoids and Apocarotenoids","volume":"73","author":"Lin","year":"2025","journal-title":"J. Agric. Food Chem."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c06012","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/50249\/66503289\/acsomega.6c06012.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/50249\/66503289\/acsomega.6c06012.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:13:08Z","timestamp":1788217988000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/33\/50249\/5252973\/Integrating-Machine-Learning-and-Transcriptomics"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":76,"journal-issue":{"issue":"33","published-online":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,8,25]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c06012","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}