Methanol biotransformation for the production of the biodegradable plastic monomer L-lactate in yeast

Methanol biotransformation for the production of the biodegradable plastic monomer L-lactate in yeast | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Methanol biotransformation for the production of the biodegradable plastic monomer L-lactate in yeast Yongjin Zhou, Wei Yu, Chenyue Zhang, Yunxia Li, Qing-An Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6079167/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Nov, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Methanol is an ideal feedstock for biomanufacturing that can be produced from CO2 in massive quantities. Methanol biotransformation to promote the production of the biodegradable plastic monomer lactate is a promising approach for mitigating white pollution in a carbon-neutral manner. However, it is still challenging to engineer microbes for lactate production from methanol because of the strong competition between product synthesis and cell growth. Here, we extensively modified the methylotrophic yeast Ogataea polymorpha to synthesize L-lactate from methanol alone and found that the cofactor ratio of NADPH/NADP+ was higher than that of NADH/NAD+ during methanol metabolism. By engineering the gene expression and cofactor preference levels of lactate dehydrogenase, enhancing cell viability, modifying cofactor homeostasis, and performing mitochondrial compartmentalization, 2.5 g/L L-lactate was produced from 10 g/L methanol in a shake flask. Fed-batch fermentation in a 1 L bioreactor resulted in the highest yield of 25.0 g/L L-lactate from methanol, which was chemically synthesized from CO2 with a yield of 0.22 g/g. A technoeconomic analysis and life cycle assessment were performed to evaluate the commercial potential of CO2-derived L-lactate, its environmental impacts, and its greenhouse gas mitigation performance. This study could lay the foundation for the carbon-neutral production of biodegradable plastic polylactic acid from CO2, thus establishing a circular economy. Biological sciences/Biotechnology/Metabolic engineering Biological sciences/Biotechnology/Industrial microbiology/Metabolic engineering Methanol biotransformation L-Lactate Cofactor engineering Mitochondrial compartmentalization Technoeconomic analysis Life cycle assessment Full Text Additional Declarations Yes there is potential Competing Interest. A patent application (2024118050174) to protect the production of L-lactate from methanol in O. polymorpha has been filed by the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, with Y.J.Z., W.Y., and J.G. named as inventors. Supplementary Files NCSI250206.pdf Dataset 1 Cite Share Download PDF Status: Published Journal Publication published 28 Nov, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6079167","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":420829733,"identity":"177a73b6-f84f-4442-be23-4d6e7ab53208","order_by":0,"name":"Yongjin Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYDACCSjN2MzA+IDHgEQtzAakaQECNgkeYnTIz24+Js1TcceuuZ33WMWbArs8BvbDDxh+7sCthXHOsTRpnjPPkhub+dJuzjFILmbgSTNg7D2DWwuzRI6ZNG/b4WTGZh6z2zwGBxIbGHIYmBnbcGthQ9ZSDNbC/wa/Fh6oFjuQFmawFgkCtkhIpCVbzjlzOAGoxVgS5Bc2iWcGB3vxaJGfkXzwxpuKw/aG/WcMP7z5Y5fHz5/88MFPPFpAgAkYHYkbGyCcBDYgcQC/BmBA/2BgsJeHchIIqR4Fo2AUjIKRBwAAqEin21geOAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-2369-3079","institution":"Dalian Institute of Chemical Physics","correspondingAuthor":true,"prefix":"","firstName":"Yongjin","middleName":"","lastName":"Zhou","suffix":""},{"id":420829734,"identity":"f01df363-0d0f-4b28-ba6c-c2ad022ce201","order_by":1,"name":"Wei Yu","email":"","orcid":"","institution":"Dalian Institute of Chemical Physics","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Yu","suffix":""},{"id":420829735,"identity":"f0e82c28-832b-4414-b160-7743b7d6498c","order_by":2,"name":"Chenyue Zhang","email":"","orcid":"","institution":"School of Chemical Engineering and Technology, Xi’an Key Laboratory of C1 Compound Bioconversion Technology, Xi'an Jiaotong University, Xi'an, P. 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