Conferring
methylotrophy on industrial microorganisms would enable
the production of diverse products from one-carbon feedstocks and
contribute to establishing a low-carbon society. Rebuilding methylotrophs,
however, requires a thorough metabolic refactoring and is highly challenging.
Only recently was synthetic methylotrophy achieved in model microorganismsEscherichia coli and baker’s yeast Saccharomyces cerevisiae. Here, we have engineered
industrially important yeast Yarrowia lipolytica to assimilate methanol. Through rationally constructing a chimeric
assimilation pathway, rewiring the native metabolism for improved
precursor supply, and laboratory evolution, we improved the methanol
assimilation from undetectable to a level of 1.1 g/L per 72 h and
enabled methanol-supported cellular maintenance. By transcriptomic
analysis, we further found that fine-tuning of methanol assimilation
and ribulose monophosphate/xylulose monophosphate (RuMP/XuMP) regeneration
and strengthening formate dehydrogenation and the serine pathway were
beneficial for methanol assimilation. This work paves the way for
creating synthetic methylotrophic yeast cell factories for low-carbon
economy.
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