Genome Mining Reveals Biosynthesis of the Antifungal Lipopeptaibols, Texenomycins, through a Hybrid PKS-NRPS System, in the Fungus Mariannaea elegans .

Texenomycins are a family of linear lipopeptaibols with a long polyketide side chain at the N-terminus and 21 amino acid residues at the C -terminus, presenting demonstrated potential as antibiotics against plant fungal pathogens. In this study, texenomycins were identified and isolated from the fungus Mariannaea elegans strain TTI-0396 and showed effective antifungal properties against two plant pathogens Colletotrichum lagenarium and Botrytis cinerea . Through analysis of the whole-genome data of M. elegans strain TTI-0396, we discovered a hybrid PKS-NRPS system with the polyketide synthase (PKS: TexQ), thioesterase (TexO), acyl-CoA ligase (TexI), and three nonribosomal peptide synthetases (NRPSs: TexG, TexJ, TexV) in the tex gene cluster that were proposed to be responsible for the biosynthesis of texenomycins and another related lipopeptaibol, lipohexin. The functions of six key genes ( texQ , texO , texI , texG, texJ , and texV ) in the hybrid PKS-NRPS system were verified by gene deletion experiments, and five genes ( texQ , texO , texI , texG , and texV ) were confirmed to be responsible for the biosynthesis of texenomycins, while four genes ( texQ , texO , texI , and texJ ) were involved in the biosynthesis of lipohexin. Furthermore, the function of one transcription factor gene ( texR ), which enhanced the production of texenomycins by regulating the key genes in the tex gene cluster, was also demonstrated through gene deletion and overexpression experiments. Finally, a hypothetical scheme for texenomycins and lipohexin biosynthesis assembly is proposed. The elucidation of this intricate hybrid PKS-NRPS system has significantly deepened our comprehension of the mechanisms underlying the generation and chemical diversity of fungal lipopeptaibol natural products, offering a promising avenue for future research and potential applications in fungicidal disease control in agriculture.