Gluconic acid-producing Pseudomonas sp. prevent γ-actinorhodin biosynthesis by Streptomyces coelicolor A3(2)

Abstract

Streptomyces are ubiquitous soil bacteria well known for their ability to produce a wide range of secondary metabolites including antibiotics. In their natural environments, they co-exist and interact with complex microbial communities and their natural products are assumed to play a major role in mediating these interactions. Reciprocally, their secondary metabolism can be influenced by the surrounding microbial communities. Little is known about these complex interactions and the underlying molecular mechanisms. During pairwise co-culture experiments, a fluorescent Pseudomonas, Pseudomonas fluorescens BBc6R8, was shown to prevent the production of the diffusible blue pigment antibiotic γ-actinorhodin by Streptomyces coelicolor A3(2) M145 without altering the biosynthesis of the intracellular actinorhodin. A mutant of the BBc6R8 strain defective in the production of gluconic acid from glucose and consequently unable to acidify the culture medium did not show any effect on the γ-actinorhodin biosynthesis in contrast to the wild-type strain and the mutant complemented with the wild-type allele. In addition, when glucose was substituted by mannitol in the culture medium, P. fluorescens BBc6R8 was unable to acidify the medium and to prevent the biosynthesis of the antibiotic. All together, the results show that P. fluorescens BBc6R8 impairs the biosynthesis of the lactone form of actinorhodin in S. coelicolor by acidifying the medium through the production of gluconic acid. Other fluorescent Pseudomonas and the opportunistic pathogen Pseudomonas aeruginosa PAO1 also prevented the γ-actinorhodin production in a similar way. We propose some hypotheses on the ecological significance of such interaction.

Discovery of a Cryptic Intermediate in Late Steps of Mithramycin Biosynthesis

“…This self-resistance mechanism appears to be an unusual strategy,facilitated by the formation of acomplex of biosynthetic enzymes potentially interacting with am embrane transport channel to avoid damage by the active natural product to the host cells.Analogy for this model can be found in the actinorhodin biosynthesis in Streptomyces coelicolor. [24] Thed iffusible,g amma form of actinorhodin is only found after passage through an RND transporter and in conjunction with abasic extracellular environment. Asimilar transportermediated catalysis may also be present in the MTM pathway, as iso-MTM has not been found in S. argillaceus cultures.…”

Role of GntR Family Regulatory GeneSCO1678in Gluconate Metabolism inStreptomyces coelicolorM145

“…This is not the first case where gluconate has abolished antibiotic production. For instance, cocultivation of S. coelicolor and Pseudomonas fluorescens BBc6R8, a producer of gluconic acid, stops ACT production [26]. Gluconate inhibits prodigiosin biosynthesis in Serratia sp.…”

Natural products in soil microbe interactions and evolution

“…84 While these studies document that these interactions can stimulate actinorhodin production, the mechanism(s) of this induction remains unknown. 85 Specically, the authors demonstrated that acidication via the Fig. Perez and co-workers 84 showed that M. xanthus is at least somewhat capable of preying on S. coelicolor.…”

“…Several species of Pseudomonas, including P. uorescens and P. aeruginosa have been shown to inhibit the production of g-actinorhodin, the diffusible blue form of the compound, by S. coelicolor. 85 Specically, the authors demonstrated that acidication via the production of gluconic acid by the Pseudomonas strains inhibited the biosynthesis of g-actinorhodin, while the production of cell-associated actinorhodin (which is red) was unchanged.…”