Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces

Abstract

The numerous secondary metabolites in Streptomyces spp. are crucial for various applications. For example, cephamycin C is used as an antibiotic, and avermectin is used as an insecticide. Specifically, antibiotic yield is closely related to many factors, such as the external environment, nutrition (including nitrogen and carbon sources), biosynthetic efficiency and the regulatory mechanisms in producing strains. There are various types of regulatory genes that work in different ways, such as pleiotropic (or global) regulatory genes, cluster-situated regulators, which are also called pathway-specific regulatory genes, and many other regulators. The study of regulatory genes that influence antibiotic biosynthesis in Streptomyces spp. not only provides a theoretical basis for antibiotic biosynthesis in Streptomyces but also helps to increase the yield of antibiotics via molecular manipulation of these regulatory genes. Currently, more and more emphasis is being placed on the regulatory genes of antibiotic biosynthetic gene clusters in Streptomyces spp., and many studies on these genes have been performed to improve the yield of antibiotics in Streptomyces. This paper lists many antibiotic biosynthesis regulatory genes in Streptomyces spp. and focuses on frequently investigated regulatory genes that are involved in pathway-specific regulation and pleiotropic regulation and their applications in genetic engineering.

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

“…The additional genes found in the mon gene cluster encode enzymes involved in isomerisation, epoxidation (MonCI), hydroxylation (MonBI, MonBII, and MonD), and methylation (MonE) of the structure to the final product monensin A [98,219]. Finally, the mon gene cluster includes three regulator genes, monH, monRI, and monRII, and the gene monT, which encodes an efflux protein, believed to confer self-resistance to the host [98,217,220,221].…”

An inhibitory compound produced by a soil isolate of Rhodococcus has strong activity against the veterinary pathogen R. equi

“…The gene BTZ20_3964, however, appears to be a Lux R “solo”: A Lux R-type transcriptional regulatory protein not associated with a matching Lux I synthase [22]. Such Lux R “solos” have been previously described as positive regulators of antibiotic biosynthesis in Streptomyces [25, 30] and could be the regulator for this Rhodococcus gene cluster as well.…”

Clavulanic Acid Production by Streptomyces clavuligerus: Insights from Systems Biology, Strain Engineering, and Downstream Processing

“…Usually, antibiotic biosynthetic clusters are regulated by two types of transcriptional regulators: pathway-specific regulators (PSRs) and pleiotropic regulators [ 86 ]. At a lower level, PSRs are located inside the antibiotic biosynthetic cluster and these proteins can bind directly to the promoters of genes in the same biosynthetic pathway [ 87 , 88 ]. Similarly, at the top level, global regulators are known to control the production of antibiotics in the Streptomyces genus [ 87 , 88 ].…”