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

Abstract Programmable control of bacterial gene expression is of great interest for both applied and academic research. This is particularly true for Gram-positive bacteria of the genus Streptomyces, major producers of prodigious natural products. Despite 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, referred to as StrepT-switch. The bio-switch enables tunable and bidirectional control of gene expression with temperature as stimulation input. StrepT-switch has been proved successful for highly efficient CRISPR/Cas9-mediated genome engineering, as well as programmable control of antibiotic production and morphology differentiation. The versatility of the device has also been exemplified by thermal induction of a site-specific relaxase ZouA-mediated DNA amplification for overproduction of actinorhodin, a blue pigmented polyketide antibiotic. This study demonstrates the exploration a temperature-sensing module and exemplifies its versatility for programmable control of various target genes in Streptomyces species.