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.