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

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.