Microbial biosynthesis provides a feasible approach to sustainably produce advanced biofuels and biochemicals from renewable feedstocks. Methanol is an ideal feedstock for bio-manufacturing since it can be massively produced from CO₂ through green energy, such as solar energy.

Recently, a joint research group led by Prof. Yongjin Zhou and Prof. Lihua Zhang engineered and optimized Pichia pastoris for bioproduction of α-bisabolene from sole methanol with the aid of proteomics. We extensively engineered industrial yeast Pichia pastoris for overproduction of bisabolene by optimizing isoprenoid biosynthetic pathway in P. pastoris cytosol and peroxisome. Quantative proteomic analysis identified that acetoacetyl-CoA thiolase was a bottleneck in peroxisomal isoprenoid biosynthetic pathway. Enhancing the expression of acetoacetyl-CoA thiolase significantly improved the α-bisabolene biosynthesis by 72%, which realized 1.1 g/L α-bisabolene production under fed-batch in shake-flask. This study provides a feasible approach for optimizing the metabolic pathway for overproduction of other chemicals from sole methanol in P. pastoris.

This study was published in JACS Au on April 29. This study was supported by the National Key Research and Development Program of China, Liaoning distinguished scholars and DICP innovation grant. (Text and image by Linhui Gao).

Link：https://doi.org/10.1021/jacsau.4c00106

中文版