High-level production of free fatty acids from lignocellulose hydrolysate by co-utilizing glucose and xylose in yeast

Lignocellulose bio-refinery via microbial cell factories for chemical production represents a renewable and sustainable route in response to resource starvation and environmental concerns. However, the challenges associated with the co-utilization of xylose and glucose often hinders the efficiency of lignocellulose bioconversion. Here, we engineered yeast <i>Ogataea polymorpha</i> to effectively produce free fatty acids from lignocellulose. The non-oxidative branch of the pentose phosphate pathway, and the adaptive expression levels of xylose metabolic pathway genes <i>XYL1</i>, <i>XYL2</i> and <i>XYL3</i>, were systematically optimized. In addition, the introduction of xylose transporter and global regulation of transcription factors achieved synchronous co-utilization of glucose and xylose. The engineered strain produced 11.2 g/L FFAs from lignocellulose hydrolysates, with a yield of up to 0.054 g/g. This study demonstrated that metabolic rewiring of xylose metabolism could support the efficient co-utilization of glucose and xylose from lignocellulosic resources, which may provide theoretical reference for lignocellulose biorefinery.