Dataset Information

Sulfane sulfur-activated actinorhodin production and sporulation is maintained by a natural gene circuit in Streptomyces coelicolor.

ABSTRACT: Sulfane sulfur, including polysulfide and persulfide, is a newly identified cellular component present in microorganisms; however, its physiological functions are unclear. Streptomyces coelicolor M145 is a model strain of actinomycetes, which produces several polyketides, including actinorhodin. Herein, we found that both exogenously added and endogenously generated sulfane sulfur increased the actinorhodin production and accelerated spore formation of S. coelicolor M145. This bacterial species carries a natural gene circuit containing four genes that encode a CsoR-like transcription factor (ScCsoR), persulfide dioxygenase (ScPDO), rhodanese and a sulfite transporter, which were shown to be responsible for sensing and removal of excessive sulfane sulfur. ScCsoR was observed to bind to the promoters of the four genes, thus repressing their transcription. Sulfane sulfur modified Cys37 of ScCsoR, and the modified ScCSoR did not bind to the promoters, thereby activating the transcription of ScPDO. The deletion of ScCsoR decreased cellular sulfane sulfur, while the deletion of ScPDO increased its levels. The increased sulfane sulfur promoted actinorhodin production and sporulation. This study unveiled a natural gene circuit for maintaining sulfane sulfur homeostasis in bacteria. Further, we identified the trigger effect of sulfane sulfur on actinorhodin production, presenting a new approach for activating polyketide gene clusters in actinomycetes.

SUBMITTER: Lu T

PROVIDER: S-EPMC7533328 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The transcription factor AdpA is a key regulator controlling both secondary metabolism and morphological differentiation in Streptomyces. Due to its critical functions, its expression undergoes multilevel regulations at transcriptional, posttranscriptional, and translational levels, yet no posttranslational regulation has been reported. Sulfane sulfur, such as hydro polysulfide (HSnH, n ≥ 2) and organic polysulfide (RSnH, n ≥ 2), is common inside microorganisms, but its physiological functions are largely unclear. Here, we discovered that sulfane sulfur posttranslationally modifies AdpA in Streptomyces coelicolor via specifically reacting with Cys62 of AdpA to form a persulfide (Cys62-SSH). This modification decreases the affinity of AdpA to its self-promoter PadpA, allowing increased expression of adpA, further promoting the expression of its target genes actII-4 and wblA. ActII-4 activates actinorhodin biosynthesis, and WblA regulates morphological development. Bioinformatics analyses indicated that AdpA-Cys62 is highly conserved in Streptomyces, suggesting the prevalence of such modification in this genus. Thus, our study unveils a new type of regulation on the AdpA activity and sheds a light on how sulfane sulfur stimulates the production of antibiotics in Streptomyces. IMPORTANCE Streptomyces species produce a myriad of natural products with (potential) clinical applications. While the database of biosynthetic gene clusters is quickly expanding, their regulation mechanisms are rarely known. Sulfane sulfur species are commonly present in microorganisms with unclear functions. Here, we discovered that sulfane sulfur increases actinorhodin (ACT) production in S. coelicolor. The underlying mechanism is that sulfane sulfur specifically reacts with AdpA, a global transcription factor controlling both ACT gene cluster and morphological differentiation-related genes, to form sulfhydrated AdpA. This modification changes the dynamics of AdpA-controlled gene networks and leads to high expression of ACT biosynthetic genes. Given the wide prevalence of AdpA and sulfane sulfur in Streptomyces, this mechanism may represent a common regulating pattern of all AdpA-controlled biosynthetic pathways. Thus, this finding provides a new strategy for mining and activating valuable biosynthetic gene clusters.

Project description:BackgroundThe sporulation of aerial hyphae of Streptomyces coelicolor is a complex developmental process. Only a limited number of the genes involved in this intriguing morphological differentiation programme are known, including some key regulatory genes. The aim of this study was to expand our knowledge of the gene repertoire involved in S. coelicolor sporulation.ResultsWe report a DNA microarray-based investigation of developmentally controlled gene expression in S. coelicolor. By comparing global transcription patterns of the wild-type parent and two mutants lacking key regulators of aerial hyphal sporulation, we found a total of 114 genes that had significantly different expression in at least one of the two mutants compared to the wild-type during sporulation. A whiA mutant showed the largest effects on gene expression, while only a few genes were specifically affected by whiH mutation. Seven new sporulation loci were investigated in more detail with respect to expression patterns and mutant phenotypes. These included SCO7449-7451 that affect spore pigment biogenesis; SCO1773-1774 that encode an L-alanine dehydrogenase and a regulator-like protein and are required for maturation of spores; SCO3857 that encodes a protein highly similar to a nosiheptide resistance regulator and affects spore maturation; and four additional loci (SCO4421, SCO4157, SCO0934, SCO1195) that show developmental regulation but no overt mutant phenotype. Furthermore, we describe a new promoter-probe vector that takes advantage of the red fluorescent protein mCherry as a reporter of cell type-specific promoter activity.ConclusionAerial hyphal sporulation in S. coelicolor is a technically challenging process for global transcriptomic investigations since it occurs only as a small fraction of the colony biomass and is not highly synchronized. Here we show that by comparing a wild-type to mutants lacking regulators that are specifically affecting processes in aerial hypha, it is possible to identify previously unknown genes with important roles in sporulation. The transcriptomic data reported here should also serve as a basis for identification of further developmentally important genes in future functional studies.

Dataset Information

Sulfane sulfur-activated actinorhodin production and sporulation is maintained by a natural gene circuit in Streptomyces coelicolor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets