Bioinformatics-directed discovery of dehydrated linear trimer and dimer of 2,3-dihydroxybenzoyl-L-serine from Streptomyces albofaciens JCM 4342

Abstract:

[Background] As an essential element for bacterial growth, iron in its ferric form is almost insoluble in aqueous environments. Bacteria have evolved to produce various siderophores to facilitate iron uptake. For Streptomyces, the characteristic siderophores are desferrioxamines, while they can also produce other structurally different siderophores, such as ceolichelin, albomycin, enterobactin, and griseobactin. [Objective] We aimed to reveal the distribution and characteristic of siderophore biosynthetic gene clusters (BGCs), and to explore their product structures in streptomycetes. [Methods] We systematically investigated the distribution and conservation of siderophore BGCs in 308 annotated Streptomyces genomes using bioinformatics tools. Chromatographic and spectroscopic methods were utilized to isolate and characterize the enterobactin-related natural products. [Results] This enabled us to identify an orphan enterobactin BGC, which lacked genes encoding enzymes for the biosynthesis of 2,3-dihydroxybenzoic acid (2,3-DHB), together with a griseobactin BGC in Streptomyces albofaciens JCM 4342 and other strains. Four enterobactin-derived natural products, including linear trimer and dimer of 2,3-dihydroxybenzoyl-L-serine (2,3-DHBS), and their dehydrated products, were identified from S. albofaciens JCM 4342. [Conclusion] These results suggested an interesting synergistic biosynthetic mechanism executed by the two BGCs. The orphan enterobactin BGC encoding enzymes hijacked the 2,3-DHB, which was biosynthesized by the griseobactin BGC, to complete biosynthesis of the four aforementioned enterobactin-related natural products.