A tunable and reversible thermo-inducible bio-switch for streptomycetes

Abstract Programmable control of bacterial gene expression holds great significance for both applied and academic research. This is particularly true for Streptomyces, a genus of Gram-positive bacteria and major producers of prodigious natural products. Despite that a few inducible regulatory systems have been developed for use in Streptomyces, there is an increasing pursuit to augment the toolkit of high-performance induction systems. We herein report a robust and reversible thermo-inducible bio-switch, designated as StrepT-switch. This bio-switch enables tunable and reversible control of gene expression using physiological temperatures as stimulation inputs. It has been proven successful in highly efficient CRISPR/Cas9-mediated genome engineering, as well as programmable control of antibiotic production and morphological differentiation. The versatility of the device is also demonstrated by thermal induction of a site-specific relaxase ZouA for overproduction of actinorhodin, a blue pigmented polyketide antibiotic. This study showcases the exploration a temperature-sensing module and exemplifies its versatility for programmable control of various target genes in Streptomyces species.