The Gram-positive filamentous soil bacteria belonging to the genus Streptomyces possess a relatively large genome. Their extensive regulatory elements and vast repertoire of secondary metabolites allow them to thrive in the extremely heterogeneous and complex soil environment. One such regulator is TipA, a MerR family type transcription factor, a putative regulator of cellular processes responding to thiopeptide antibiotics and metal stress.

The responses of S. coelicolor A3 (2) and S. mirabilis P16B-1 to thiostrepton and metal were investigated. RNA-Seq analysis comparing wild type and a tipA knockout in both species revealed significant changes in the expression of genes involved in cobalamin biosynthesis under either nickel or thiostrepton stress, depending on the presence of TipA. The cobalt containing cobalamin, or vitamin B12, acts as a coenzyme for multiple proteins but also is known to regulate gene translation via a riboswitch mechanism. Differences in selected cobalamin synthesis gene expression between wild type and knockout strain were confirmed in S. coelicolor A3(2) via qPCR. Less cobalamin was extracted from S. coelicolor A3(2) cultures treated with either nickel or copper, although this response, unlike the observations on RNA level, did not depend on the presence of TipA. Analysis of cellular metal content revealed that the presence of TipA significantly impacts the concentration of cobalt, iron and nickel in cells of S. coelicolor A3(2) but not S. mirabilis P16B-1 under thiostrepton stress.

The auxotrophic soil community members depend on the vitamins produced by other organisms. Additionally, metals and antibiotics play a role in structuring the soil microbiome. In this context, cobalamin may serve as a common good produced by Streptomyces. Understanding the regulatory response of Streptomyces to various environmental stressors, particularly in the context of TipA presence, could provide insights into the possibility of thiopeptides being involved in microbial communication and the ecological role of Streptomyces within soil habitats.