Evolutionary engineering of <i>Saccharomyces cerevisiae</i>: Crafting a synthetic methylotroph via self-reprogramming.

ABSTRACT: Methanol, as a non-edible feedstock, offers a promising sustainable alternative to sugar-based substrates in biochemical production. Despite progress in engineering methanol assimilation in nonmethylotrophs, the full transformation into methanol-dependent synthetic methylotrophs remains a formidable challenge. Here, moving beyond the conventional rational design principle, we engineered a synthetic methylotrophic Saccharomyces cerevisiae through genome rearrangement and adaptive laboratory evolution. This evolutionarily advanced strain unexpectedly shed the heterologous methanol assimilation pathway and demonstrated the robust growth on sole methanol. We discovered that the evolved strain likely realized methanol assimilation through a previously unidentified Adh2-Sfa1-rGly (ASrG) p

SUBMITTER: Guo F 

PROVIDER: S-EPMC11661404 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature