Advances in engineering methylotrophic yeast for biosynthesis of valuable chemicals from methanol

Methylotrophic yeasts and bacteria, which can use methanol as carbon and energy source, have been wildly used as microbial cell factories for biomanufacturing. Due to their robustness in industrial harsh conditions, methylotrophic yeasts such as Pichia pastoris have been explored as a cell factory for production of proteins and high-value chemicals. Methanol utilization pathway (MUT) is highly regulated for efficient methanol utilization, and the downstream pathways need extensively constructed and optimized toward target metabolite biosynthesis. Here, we present an overview of methanol metabolism and regulation in methylotrophic yeasts, among which we focus on the regulation of key genes involved in methanol metabolism. Besides, the recent progresses in construction and optimization of downstream biosynthetic pathways for production of high value chemicals, such as polyketides, fatty acids and isoprenoids, are further summarized. Finally, we discuss the current challenges and feasible strategies toward constructing efficient methylotrophic cell factories may promote wide applications in the future.