Coupling of secondary metabolite production in Bacillus subtilis

Although not essential for their growth, the production of secondary metabolites increases the fitness of the producing microorganisms in their natural habitat by enhancing establishment, competition and nutrient acquisition. The Gram-positive soil-dwelling bacterium, Bacillus subtilis produces a variety of secondary metabolites. Here, we investigated the regulatory relationship between the non-ribosomal peptide surfactin and the sactipeptide bacteriocin subtilosin A. We discovered that B. subtilis mutants lacking surfactin production exhibited higher production of subtilosin A compared to their parental wild-type strain. Additionally, spatial visualization of B. subtilis production of metabolites demonstrated that surfactin secreted by a wild-type colony could suppress subtilosin A production in an adjacent mutant colony lacking surfactin production. Reporter assays were performed using mutants in specific transcriptional regulators that confirmed the role of ResD as an activator of the subtilosin A encoding BGC, while removal or Rok and AbrB repressors increased expression of the BGC that was further enhanced by additional deletion of surfactin, suggesting that a so far unidentified regulator might mediate the influence of surfactin on production of subtilosin A. Our study reveals a regulatory influence of one secondary metabolite on another, highlighting that the function of secondary metabolites could be more complex than its influence on other organisms and interactions among secondary metabolites could also contribute to their ecological significance. ImportanceSecondary metabolites play an important role in the life of microorganisms facilitating their fitness in the environment, including competing against other microorganisms, interacting with their host or environment, and allowing expansion in their environment. However, secondary metabolites also function as cue molecules influencing gene expression between and within species. Here, we describe that the non-ribosomally synthesized peptide surfactin repress the production of ribosomally synthesized and post translationally modified peptide, subtilosin A in Bacillus subtilis, revealing an ecological interaction between two secondary metabolites that could potentially influence the biocontrol efficiency of B. subtilis strain that depends on the production of these secondary metabolites against plant pathogen microorganisms.