Abstract
The regulatory role of redox-sensing regulator Rex was investigated in Streptomyces avermitilis. Eleven genes/operons were demonstrated to be directly regulated by Rex; these genes/operons are involved in aerobic metabolism, morphological differentiation, and secondary metabolism. Rex represses transcription of target genes/operons by binding to Rex operator (ROP) sequences in the promoter regions. NADH reduces DNA-binding activity of Rex to target promoters, while NAD+ competitively binds to Rex and modulates its DNA-binding activity. Rex plays an essential regulatory role in aerobic metabolism by controlling expression of the respiratory genes atpIBEFHAGDC, cydA1B1CD, nuoA1-N1, rex-hemAC1DB, hppA, and ndh2. Rex also regulates morphological differentiation by repressing expression of wblE, which encodes a putative WhiB-family transcriptional regulator. A rex-deletion mutant (Drex) showed higher avermectin production than the wild-type strain ATCC31267, and was more tolerant of oxygen limitation conditions in regard to avermectin production.
Highlights
Even though Rex was first characterized in S. coelicolor and its regulatory mechanism has been extensively studied, few target operons/genes of Rex in Streptomyces have been confirmed[4], and the overall regulatory function of Rex in this genus remains to be elucidated
We investigated the regulatory role of Rex in the expression of operons/genes involved in aerobic metabolism, morphology, and secondary metabolism of S. avermitilis
AtpIBEFHAGDC, cydA1B1CD, nuoA1-N1, and rex-hemAC1DB operons encode key components of the electron transfer chain and play crucial roles in aerobic metabolism14–17. hppA encodes a putative pyrophosphate-energized proton pump that converts energy from pyrophosphate hydrolysis into active H+ transport across the plasma membrane18. ndh[2] encodes a NADH dehydrogenase involved in NAD+ regeneration19,20. echA7 encodes an enoyl-CoA hydratase that catalyzes the second step of the β-oxidation pathway of fatty acid metabolism[21]
Summary
Even though Rex was first characterized in S. coelicolor and its regulatory mechanism has been extensively studied, few target operons/genes of Rex in Streptomyces have been confirmed[4], and the overall regulatory function of Rex in this genus remains to be elucidated. S. avermitilis is an important species used for industrial production of avermectins, a group of anthelmintic antibiotics widely used in the medical, veterinary, and agricultural fields[11]. We investigated the regulatory role of Rex in the expression of operons/genes involved in aerobic metabolism, morphology, and secondary metabolism of S. avermitilis. Our findings have potential application to novel genetic engineering strategies for high antibiotic-producing strains and hypoxia-tolerating strains of this genus
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