Lignocellulosic biomass has been widely recognized as a renewable feedstock for 2nd-generation biomanufacturing. A key challenge in this field is finding an efficient way to co-ferment mixed glucose and xylose in lignocellulosic hydrolysates, as it is crucial for lowering the cost of the final products. However, due to limited xylose assimilation and the glucose repression effect, the co-utilization of glucose and xylose in microbes has proven to be a challenging task.
A research group led by Prof. Zhou Yongjin from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) has recently developed a microbial platform for lignocellulose bio-refinery. This ground-breaking platform enables the efficient synthesis of acetyl-CoA derivatives, including fatty acids (FFA), and 3-hydroxypropionic acid (3-HP), by rewiring the cellular metabolism of Ogataea (Hansenula) polymorpha. In their study, published in Nature Chemical Biology on Aug. 24, the researchers demonstrated the co-utilization of glucose and xylose without compromising the native glucose metabolism.
To achieve efficient co-fermentation of glucose and xylose, the researchers made several genetic modifications to the microbial strain. They introduced a hexose transporter mutant and xylose isomerase to facilitate xylose assimilation and import. Additionally, they overexpressed the native xylulokinase to enhance xylose catabolism. These strategic modifications enabled the engineered strain to produce impressive amounts of FFA. In shake flasks, the strain produced 7.0 g/L FFA from real lignocellulosic hydrolysates, while in a bioreactor, it achieved a remarkable 38.2 g/L FFA from simulated lignocellulose.
Building upon their success with FFA production, the research team further expanded the capabilities of the cell factory to produce a different value-added chemical known as 3-HP. They achieved this by implementing a metabolic transforming strategy, which allowed them to obtain the highest 3-HP titer of 79.6 g/L from simulated lignocellulose. This breakthrough in product diversification highlights the potential of Ogataea (Hansenula) polymorpha as an incredibly versatile cell factory for producing a wide range of valuable chemicals from lignocellulosic biomass.
Prof. Zhou and his team’s work represents a significant breakthrough in the field of co-fermentation of glucose and xylose in lignocellulosic biomass. By developing a microbial platform that efficiently synthesizes acetyl-CoA derivatives, they have addressed the challenges associated with limited xylose assimilation and glucose repression effects. The successful co-utilization of glucose and xylose, demonstrated without compromising the native glucose metabolism, opens up exciting possibilities for the production of various value-added chemicals from lignocellulosic biomass. This research paves the way for more sustainable and cost-effective biomanufacturing processes, contributing to the realization of a greener and more sustainable future.