Methanol is an ideal biomanufacturing feedstock that can benefit global carbon neutrality. However, the toxicity of methanol limits the efficiency of methanol metabolism toward biochemical production.

Recently, a research group led by Prof. ZHOU Yongjin from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) has shown that engineering production of free fatty acids from sole methanol results in cell death with decreased cellular levels of phospholipids in the methylotrophic yeast Ogataea polymorpha, and cell growth is restored by adaptive laboratory evolution.

The team successfully engineered yeast Ogataea polymorpha for efficient production of free fatty acids (FFA) from sole methanol by rewiring cellular metabolism and relieving the methanol toxicity.

As a common ingredient in baking and brewing, yeast is a perfect host for methanol-based bio-manufacturing. The efficiency of the biosynthetic process may be constrained by methanol toxicity, as cellular methanol metabolism is strictly controlled. There is limited information on methanol toxicity, metabolism, and product biosynthesis.

Scientists observed growth deficiency of engineered FFA producing Ogataea polymorpha in methanol, and this deficiency was restored by adaptive laboratory evolution. Multi-omics analysis (genomics, transcriptomics, and lipidomics) showed that FFA overproduction perturbed phospholipid hemostasis.

Prof. ZHOU said, “This work reveals the mechanisms of methanol toxicity during bio-productions and achieves efficient methanol biotransformation to value-added products for industrial applications.”

Journal Reference:

  1. Gao, J., Li, Y., Yu, W. et al. Rescuing yeast from cell death enables overproduction of fatty acids from sole methanol. Nat Metab 4, 932–943 (2022). DOI: 10.1038/s42255-022-00601-0