Abstract
Microbial coculture to mimic the ecological habitat has been suggested as an approach to elucidate the effect of microbial interaction on secondary metabolite biosynthesis of Streptomyces. However, because of chemical complexity during coculture, underlying mechanisms are largely unknown. Here, we found that iron competition triggered antibiotic biosynthesis in Streptomyces coelicolor during coculture with Myxococcus xanthus. During coculture, M. xanthus enhanced the production of a siderophore, myxochelin, leading M. xanthus to dominate iron scavenging and S. coelicolor to experience iron-restricted conditions. This chemical competition, but not physical contact, activated the actinorhodin biosynthetic gene cluster and the branched-chain amino acid degradation pathway which imply the potential to produce precursors, along with activation of a novel actinorhodin export system. Furthermore, we found that iron restriction increased the expression of 21 secondary metabolite biosynthetic gene clusters (smBGCs) in other Streptomyces species. These findings suggested that the availability for key ions stimulates specific smBGCs, which had the potential to enhance secondary metabolite biosynthesis in Streptomyces.
Highlights
IntroductionTremendous efforts have focused on awakening the silent Streptomyces secondary metabolite biosynthetic gene clusters (smBGCs), including media optimization, epigenetic modifier treatment, mutagenesis, and genetic engineering [5,6,7]
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.Streptomyces, ubiquitous soil gram-positive bacteria, are well-known for their ability to produce diverse secondary metabolites, including many compounds that are currently in clinical use [1]
In addition to these approaches, accurately mimicking natural habitats is challenging, microbial coculture of two or more different microorganisms in which bacterial populations cohabitate with complex communities, is an effective approach to understand the ecological roles of the chemical diversity of Streptomyces and to turn on their cryptic pathways [8, 9]
Summary
Tremendous efforts have focused on awakening the silent Streptomyces smBGCs, including media optimization, epigenetic modifier treatment, mutagenesis, and genetic engineering [5,6,7]. In addition to these approaches, accurately mimicking natural habitats is challenging, microbial coculture of two or more different microorganisms in which bacterial populations cohabitate with complex communities, is an effective approach to understand the ecological roles of the chemical diversity of Streptomyces and to turn on their cryptic pathways [8, 9]. Precise characterization of the microbial interaction governed by secondary metabolites will uncover the unexplored ecological systems and provide accurate selection pressure for improving the industrial production of secondary metabolites
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