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Free keywords:
*Bacteria/genetics
Humans
Multigene Family
*Polyketide Synthases/genetics
Virulence
Abstract:
Piscibactins and photoxenobactins are metallophores and virulence factors, whose biosynthetic gene cluster, termed pxb, is the most prevalent polyketide synthase/non-ribosomal peptide synthetase hybrid cluster across entomopathogenic bacteria. They are structurally similar to yersiniabactin, which contributes to the virulence of the human pathogen Yersinia pestis. However, the pxb-derived products feature various chain lengths and unusual carboxamide, thiocarboxylic acid, and dithioperoxoate termini, which are rarely found in thiotemplated biosyntheses. Here, we characterize the pxb biosynthetic logic by gene deletions, site-directed mutagenesis, and isotope labeling experiments. Notably, we propose that it involves (1) heterocyclization domains with various catalytic efficiencies catalyzing thiazoline and amide/thioester bond formation and (2) putative C-N and C-S bond cleavage off-loading manners, which lead to products with different chain lengths and usual termini. Additionally, the post-assembly-line spontaneous conversions of the biosynthetic end product contribute to production titers of the other products in the culture medium. This study broadens our knowledge of thiotemplated biosynthesis and how bacterial host generate a chemical arsenal.
