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 produced from CO₂ through green energy, such as solar energy.

Recently, a research group led by Prof. ZHOU Yongjin and Prof. ZHANG Lihua from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) engineered and optimized Pichia pastoris for bioproduction of α-bisabolene from sole methanol with the aid of proteomics. This study was published in JACS Au on April 29.

The researchers extensively engineered industrial yeast Pichia pastoris for overproduction of bisabolene by optimizing isoprenoid biosynthetic pathway in Pichia pastoris cytosol and peroxisome.

Through quantitative proteomic analysis, they have identified that acetoacetyl-CoA thiolase was a bottleneck in the peroxisomal isoprenoid biosynthetic pathway. And they enhanced the expression of acetoacetyl-CoA thiolase to improve the α-bisabolene biosynthesis by 100%, 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 Pichia pastoris.

"Engineering α-bisabolene production from sole methanol might provide a sustainable approach for advanced biofuel production," Prof. ZHOU said. "We here clearly showed that proteomic analysis can help to optimize the biosynthetic pathway by identifying the pathway bottleneck," Prof. ZHANG said.