Functional Expression of SAV3818, a Putative TetR-Family Transcriptional Regulatory Gene from Streptomyces avermitilis, Stimulates Antibiotic Production in Streptomyces Species

Abstract

Avermectin and its analogs are major commercial antiparasitic agents in the fields of animal health, agriculture, and human infections. Previously, comparative transcriptome analysis between the low-producer S. avermitilis ATCC31267 and the high-producer S. avermitilis ATCC31780 using a S. avermitilis whole genome chip revealed that 50 genes were overexpressed at least twofold higher in S. avermitilis ATCC31780. To verify the biological significance of some of the transcriptomics-guided targets, five putative regulatory genes were individually cloned under the strong-andconstitutive promoter of the Streptomyces expression vector pSE34, followed by the transformation into the lowproducer S. avermitilis ATCC31267. Among the putative genes tested, three regulatory genes including SAV213, SAV3818, and SAV4023 exhibited stimulatory effects on avermectin production in S. avermitilis ATCC31267. Moreover, overexpression of SAV3818 also stimulated actinorhodin production in both S. coelicolor M145 and S. lividans TK21, implying that the SAV3818, a putative TetR-family transcriptional regulator, could be a global upregulator acting in antibiotic production in Streptomyces species.

GouR, a TetR Family Transcriptional Regulator, Coordinates the Biosynthesis and Export of Gougerotin in Streptomyces graminearus

“…The production of antibiotics is subject to hierarchical control of regulators, including cluster-situated regulators, pleiotropic regulators, and global regulators (1). Among them, TetR family transcriptional regulators constitute some of the most frequently occurring transcriptional regulators and serve as both repressors (2)(3)(4)(5) and activators (6,7). TetR, the founder member of this family of regulators, is a repressor of divergently transcribed tetA, which encodes a tetracycline efflux pump.…”

Increasing Avermectin Production in Streptomyces avermitilis by Manipulating the Expression of a Novel TetR-Family Regulator and Its Target Gene Product

“…Among 115 TFRs in S. avermitilis, our group has characterized SAV151 (26), SAV576 (27), SAV577 (28), and SAV7471 (homologous to SCO0772 in S. coelicolor) (29) to be negative regulators of avermectin production. SAV3818 (homologous to SCO4421) (30) and SAV3703 (AvaR3, a ␥-butyrolactone autoregulator receptor) (23) are positive regulators of avermectin production. The other 109 TFRs remain to be characterized.…”