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

[Image: see text] Xenocoumacin 1 (Xcn1), a major antimicrobial compound produced by Xenorhabdus nematophila 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 Bacillus subtilis and Alternaria solani 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 X. nematophila CB6, which could promote the discovery of new antibiotics.