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Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast.

Xiaoxin ZhaiJiaoqi GaoYunxia LiMartin GriningerYongjin J Zhou
Published in: Proceedings of the National Academy of Sciences of the United States of America (2023)
Methanol is an ideal feedstock for chemical and biological manufacturing. Constructing an efficient cell factory is essential for producing complex compounds through methanol biotransformation, in which coordinating methanol use and product synthesis is often necessary. In methylotrophic yeast, methanol utilization mainly occurs in peroxisomes, which creates challenges in driving the metabolic flux toward product biosynthesis. Here, we observed that constructing the cytosolic biosynthesis pathway resulted in compromised fatty alcohol production in the methylotrophic yeast Ogataea polymorpha . Alternatively, peroxisomal coupling of fatty alcohol biosynthesis and methanol utilization significantly improved fatty alcohol production by 3.9-fold. Enhancing the supply of precursor fatty acyl-CoA and cofactor NADPH in the peroxisomes by global metabolic rewiring further improved fatty alcohol production by 2.5-fold and produced 3.6 g/L fatty alcohols from methanol under fed-batch fermentation. We demonstrated that peroxisome compartmentalization is helpful for coupling methanol utilization and product synthesis, and with this approach, constructing efficient microbial cell factories for methanol biotransformation is feasible.
Keyphrases
  • carbon dioxide
  • fatty acid
  • cell wall
  • alcohol consumption
  • single cell
  • saccharomyces cerevisiae
  • room temperature
  • cell therapy
  • stem cells
  • mesenchymal stem cells
  • anaerobic digestion