Lignocellulosic biomass is a valuable renewable feedstock for second-generation biomanufacturing. However, the efficient co-fermentation of mixed glucose and xylose in lignocellulosic hydrolysates presents a major challenge due to limited xylose assimilation and the glucose repression effect. In a recent study published in Nature Chemical Biology, a research group led by Prof. Zhou Yongjin from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) proposed a microbial platform for lignocellulose bio-refinery that addresses these issues.
The researchers successfully achieved co-utilization of glucose and xylose by implementing innovative strategies. They introduced a hexose transporter mutant and xylose isomerase, and overexpressed the native xylulokinase to enhance xylose catabolism and import. These genetic modifications resulted in an engineered strain that exhibited improved capabilities for synthesizing acetyl-CoA derivatives, specifically fatty acids (FFA) and 3-hydroxypropionic acid (3-HP).
The engineered strain demonstrated impressive performance in terms of FFA production. In shake flasks, it produced 7.0 g/L FFA from real lignocellulosic hydrolysates, and in a bioreactor, it achieved a remarkable FFA production of 38.2 g/L from simulated lignocellulose. Furthermore, the researchers expanded the application of this superior cell factory for 3-HP production using a metabolic transforming strategy. The engineered strain achieved the highest 3-HP titer of 79.6 g/L from simulated lignocellulose.
Prof. Zhou emphasized that this work not only realized the co-utilization of xylose and glucose without compromising native glucose metabolism but also demonstrated the potential of Ogataea (Hansenula) polymorpha as a versatile cell factory for producing valuable chemicals from lignocellulose. These findings represent a significant step towards reducing the costs associated with lignocellulosic biomass utilization in biomanufacturing processes.
The ability to efficiently co-ferment glucose and xylose is crucial for the economic feasibility of lignocellulosic bio-refineries. The microbial platform developed by Prof. Zhou’s research group offers a promising solution to this challenge. By enhancing the supply of precursor acetyl-CoA and cofactor NADPH through rewiring the cellular metabolism of O. polymorpha, the researchers have achieved significant improvements in FFA and 3-HP production. These value-added chemicals have various applications in industries such as biofuels, pharmaceuticals, and bioplastics.
The co-utilization of glucose and xylose in lignocellulosic hydrolysates has long been a hurdle in achieving cost-effective biomanufacturing processes. However, the innovative microbial platform developed by Prof. Zhou Yongjin and his team at DICP has overcome this challenge. Their engineered strain of O. polymorpha effectively co-utilizes glucose and xylose, leading to impressive production of valuable acetyl-CoA derivatives from lignocellulose. This breakthrough has opened up new possibilities for the utilization of lignocellulosic biomass in various industries, bringing us closer to a more sustainable and efficient future.
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