Enhancing the production of Xenocoumacin 1 in Xenorhabdus nematophila CB6 by a combinatorial engineering strategy

Title : Enhancing the production of Xenocoumacin 1 in Xenorhabdus nematophila CB6 by a combinatorial engineering strategy

Abstract:

Xenocoumacin 1 (Xcn1) is an excellent antimicrobial natural product against Phytophthora capsici. However, the commercial development of Xcn1 is hindered by the low yield, which results in high application cost. In this study, multiple metabolic strategies, including blocking the degradation pathway, promoter engineering and deletion of competing biosynthetic gene clusters (BGCs), were employed to improve the production of Xcn1, which was increased from 0.07 g/L to 0.91 g/L. The formation of Xcn1 reached 1.94 g/L in the TB medium with the final strain T3 in shake flask, and further reached 3.52 g/L in a 5-L bioreactor, which is the highest yield ever reported. The engineered strain provides a valuable platform for production of Xcn1, and the possible commercial development of the bio-fungicide. We anticipate that the metabolic engineering strategies utilized in this study and the constructed constitutive promoter library can be widely applied to other bacteria of the genera Xenorhabdus and Photorhabdus.

Keywords: Xenorhabdus nematophila, Xenocoumacin 1, Constitutive promoters, Metabolic engineering

Biography:

Guangyue Li is a professor at the Institute of Plant Protection, Chinese Academy of Agricultural Sciences. His research primarily focuses on the discovery of antimicrobial nature products in symbiotic bacteria of entomopathetic nematodes. He also works on optimizing metabolic pathways and engineering key enzymes within these pathways. From 2010 to 2014, he pursued his PhD degree at the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences. After that, from 2014 to 2017, he worked as a postdoctoral researcher in Professor Manfred. T. Reetz's laboratory at the Max Planck Institute for Coal Research in Germany. In November 2017, he returned to China and joined the Institute of Plant Protection, Chinese Academy of Agricultural Sciences.