Lignocellulose bio-refinery for chemical overproduction in yeast


Lignocellulosic biomass is a renewable feedstock for 2nd-generation biomanufacturing. In particular, efficient co-fermentation of mixed glucose (C6) and xylose (C5) sugars in lignocellulosic hydrolysates is considered one of the key issues in reducing product costs. However, it is challenging to engineer the co-utilization of xylose and glucose in microbes due to limited xylose assimilation and the glucose repression effect.

Recently, our group has proposed a microbial platform for lignocellulose bio-refinery, enabling the efficient productions of fatty acids (FFA) and 3-hydroxypropionic acid (3-HP).This microbial platform strain could efficiently synthesize acetyl-CoA derivatives, such as FFA and 3-HP, owing to the enhanced supply of precursor acetyl-CoA and cofactor NADPH by rewiring the cellular metabolism of Ogataea (Hansenula) polymorpha. On this basis, we achieved the co-utilization of glucose and xylose by introducing a hexose transporter mutant and xylose isomerase, and overexpressing the native xylulokinase to enhance xylose catabolism and import. The engineered strain produced 7.0 g/L FFA from real lignocellulosic hydrolysates in shake flasks and 38.2 g/L FFA from simulated lignocellulose in a bioreactor. Furthermore, this superior cell factory was expanded for 3-HP production by a metabolic transforming strategy, obtaining the highest 3-HP titer of 79.6 g/L from simulated lignocellulose. Therefore, our proposed platform strain and strategy could more efficiently and effectively produce target products through simple genetic manipulation from glucose and xylose in a synchronous manner.

This work achieves the co-utilization of xylose and glucose without compromising the native glucose metabolism and demonstrated the great potential of O. polymorpha as a cell factory to produce versatile value-added chemicals from lignocellulose.This study was published in Nature Chemical Biology on 24 August, 2023.The study was supported by the National Natural Science Foundation of China, and DICP innovation grant from Dalian Institute of Chemical Physics, CAS. (Test and Image by Jiaoqi Gao and We Yu)