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

Wei Yu, Chenyue Zhang, Yunxia Li, Qing-An Chen, Qiang Fei (), Jiaoqi Gao () and Yongjin J. Zhou ()
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Wei Yu: Chinese Academy of Sciences, Division of Biotechnology, Dalian Institute of Chemical Physics
Chenyue Zhang: Xi’an Jiaotong University, Xi’an Key Laboratory of C1 Compound Bioconversion Technology, School of Chemical Engineering and Technology
Yunxia Li: Chinese Academy of Sciences, Division of Biotechnology, Dalian Institute of Chemical Physics
Qing-An Chen: Chinese Academy of Sciences, Laboratory of Fine Chemicals, Dalian Institute of Chemical Physics
Qiang Fei: Xi’an Jiaotong University, Xi’an Key Laboratory of C1 Compound Bioconversion Technology, School of Chemical Engineering and Technology
Jiaoqi Gao: Chinese Academy of Sciences, Division of Biotechnology, Dalian Institute of Chemical Physics
Yongjin J. Zhou: Chinese Academy of Sciences, Division of Biotechnology, Dalian Institute of Chemical Physics

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Methanol is an ideal feedstock for biomanufacturing, and production of the biodegradable plastic monomer lactate from methanol is a promising approach for mitigating white pollution. However, it is challenging to engineer microbes for lactate production from methanol because of strong competition between product synthesis and cell growth. Here, Ogataea polymorpha is rewired to synthesize L-lactate from methanol, where the cofactor ratio of NADPH/NADP+ is higher than that of NADH/NAD+. By engineering gene expression, enhancing cell viability, modifying cofactor homeostasis, and performing mitochondrial compartmentalization, 2.5 g/L L-lactate is produced in a shake flask. Fed-batch fermentation in a bioreactor results in the highest titer of 25.0 g/L L-lactate from methanol, which is chemically synthesized from CO2. A techno-economic analysis and life cycle assessment are performed to evaluate the commercial potential, environmental impacts, and greenhouse gas mitigation performance of CO2-derived L-lactate. This study could lay the foundation for the carbon-neutral production of biodegradable plastic polylactic acid from CO2.

Date: 2025
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DOI: 10.1038/s41467-025-65793-x

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