Improving the Yield of Xenocoumacin 1 Enabled by In Situ Product Removal

Abstract

Xenocoumacin 1 (Xcn1), a major antimicrobial compound produced by <i>Xenorhabdus nematophila</i> CB6, has great potential to be developed into a novel biofungicide. However, its low yield in the producing cells has limited its possible commercial applications. In this study, we explored the effect of in situ product removal (ISPR), a well-established recovery technique, with the use of macroporous resin X-5 on the production of Xcn1 in a fermentation setting. Relative to the routine fermentation process, the yield of Xcn1 was improved from 42.5 to 73.8 μg/mL (1.7-fold) and 12.9 to 60.3 μg/mL (4.7-fold) in three and ten days, respectively. By agar diffusion plate and growth inhibition assays, the antibiotic activity against <i>Bacillus subtilis</i> and <i>Alternaria solani</i> was also found to be improved. Further study revealed that protection of Xcn1 against degradation and decrease in cell self-toxicity as well as upregulation of biosynthesis-related genes of Xcn1 at the transcription level contributed to yield improvement of Xcn1. In addition, resin X-5 significantly altered the metabolite profile of <i>X. nematophila</i> CB6, which could promote the discovery of new antibiotics.