The XRE-DUF397 Protein Pair, Scr1 and Scr2, Acts as a Strong Positive Regulator of Antibiotic Production in Streptomyces.

Ramón I Santamaría,Margarita Díaz,Jesús Martín,Laura Sevillano,Olga Genilloud,Ignacio González

doi:10.3389/fmicb.2018.02791

Abstract

The xenobiotic response element (XRE) transcription factors belong to a regulator family frequently found in Streptomyces that are often followed by small proteins with a DUF397 domain. In fact, the pair XRE-DUF397 has been proposed to comprise toxin–antitoxin (TA) type II systems. In this work, we demonstrate that one of these putative TA-systems, encoded by the genes SCO4441 and SCO4442 of Streptomyces coelicolor, and denominated Scr1/Scr2 (which stands for S. coelicolor regulator), does not behave as a toxin–antitoxin system under the conditions used as was originally expected. Instead the pair Scr1/Scr2 acts as a strong positive regulator of endogenous antibiotic production in S. coelicolor. The analysis of the 19 Streptomyces strains tested determined that overexpression of the pair Scr1/Scr2 drastically induces the production of antibiotics not only in S. coelicolor, but also in Streptomyces lividans, Streptomyces peucetius, Streptomyces steffisburgensis and Streptomyces sp. CA-240608. Our work also shows that Scr1 needs Scr2 to exert positive regulation on antibiotic production.

Highlights

Streptomyces are Gram-positive bacteria with a complex life cycle that includes the formation of mycelia and spores
Tü49, S. griseus ATCC13273, S. lividans 1326, S. parvulus JI2283, S. peucetius ATCC 27952, S. rochei CECT 3329, S. steffisburgensis NRRL3193, S. vinaceus JI2838, and 8 Streptomyces sp. strains isolated from different soil samples (Supplementary Table S1)
Routine plasmid construction and plasmid isolation was done in Escherichia coli DH5α, and E. coli ET12567, a non-methylating strain, was used to obtain the plasmids to be transformed into S. coelicolor

Summary

Introduction

Streptomyces are Gram-positive bacteria with a complex life cycle that includes the formation of mycelia and spores. In order to compete with other inhabitants of their ecosystems (mainly the soil), these bacteria have developed the capacity to produce a high number of extracellular hydrolytic enzymes and, secondary metabolites with antibiotic and antifungal activities among others (Chater, 2016). The production of these metabolites is tightly regulated through a large number of signal transduction proteins, including transcriptional regulators, which confer Streptomyces with the ability to rapidly respond to environmental changes by using available nutrients and producing secondary metabolites.

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Results

Conclusion