Identification of Fcl-29 as an Effective Antifungal Natural Product against Fusarium graminearum and Combinatorial Engineering Strategy for Improving Its Yield

Fusarium head blight (FHB), caused by Fusarium graminearum, whose occurrence and prevalence causes 10-70% wheat production loss, is one of the most destructive diseases influencing the production of wheat globally. To identify the potential natural products (NPs) against F. graminearum, we screened 59 Xenorhabdus strains and discovered that the cell-free supernatant (CFS) of X. budapestensis 14 (XBD14) displays the highest bioactivity. Multiple genetic methods coupled with HRMS/MS analysis determined the major antifungal NP to be Fcl-29, a fabclavine derivative. Fcl-29 was found to effectively control FHB of wheat in the field test and demonstrated broad-spectrum antifungal activity against important pathogenic fungi. The production of Fcl-29 was dramatically improved by 33.82-fold with the combinatorial strategy of genetic engineering (1.66-fold) and fermentation engineering (20.39-fold). The exploration of a new biofungicide in global plant protection is now possible.

Automated summary

Fusarium graminearum, the causal agent of Fusarium head blight (FHB), has a significant impact on global wheat production, resulting in 10-70% loss. In this study, we screened 59 Xenorhabdus strains and found that the cell-free supernatant (CFS) of X. budapestensis 14 (XBD14) exhibited the highest bioactivity against F. graminearum. Through genetic methods and HRMS/MS analysis, Fcl-29, a fabclavine derivative, was identified as the major antifungal natural product. Field tests demonstrated that Fcl-29 effectively controlled FHB and showed broad-spectrum antifungal activity against important pathogenic fungi. The production of Fcl-29 was significantly improved by 33.82-fold through a combinational strategy of genetic and fermentation engineering. This research opens up new possibilities for the development of biofungicides in global plant protection.