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[4GteX-12-KL]Carbon neutral overproduction of chemicals from methanol

○Yongjin Zhou1 (1. Dalian Institute of Chemical Physics, CAS (China))
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Keywords:

Metabolic Engineering,Methanol biotransformation,Yeast

Methanol is a promising one-carbon substrate for industrial bio-manufacturing. However, the cytotoxic effects of methanol and its oxidized product formaldehyde impede the methanol based bioproduction, and enhancing the robustness of strains during methanol metabolism remains a significant challenge. In this study, we enhanced the methanol tolerance of yeast Pichia pastoris through adaptive evolution and reversal metabolic engineering. Omics and morphological analyses revealed that balanced methanol metabolism, cellular homeostasis as well as efficient DNA repair are crucial for alleviating the stress associated with high methanol concentrations. Further metabolic engineering of methanol tolerance chassis enabled high-level production of free fatty acids (31 g/L) and 3-hydroxypropionic acid (127 g/L), which was much higher than that from sugars. Life cycle assessment further showed this methanol biotransformation procedure has high potential in carbon-negative biomanufacturing chemicals for industrial applications.

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