A polyketide biosynthetic gene cluster from Streptomyces antibioticus includes a LysR-type transcriptional regulator

Abstract

In the search for Type II polyketide synthases (PKSs) a DNA fragment was isolated from Streptomyces antibioticus ATCC 11891 (a producer of oleandomycin). DNA sequencing of the cloned fragment revealed six complete ORFs whose deduced products showed similarities to those of other genes known to be involved in polyketide biosynthesis. Several S. coelicolor strains mutated in different steps of actinorhodin biosynthesis (actI, actIII, actV A and actVII) were complemented by the cloned genes, suggesting that the isolated genes encode an aromatic polyketide of unknown structure and function. The cluster also contains a putative LysR-type transcriptional regulator (ORF0), which controls PKS gene expression in a heterologous host. DNA binding assays and transcriptional analysis suggest that the pathway-specific regulator for actinorhodin biosynthesis (actII-ORF4) is also involved in the expression of the cloned PKS in the host strain.

Acidic pH shock induces the expressions of a wide range of stress-response genes

“…Such enhanced expression of this regulator is considered to have led to the activation of other genes in the actinorhodin gene cluster. Genes responsible for polyketide synthesis function for actinorhodin production, ketoacylreductase ( actIII ), polyketide beta-ketoacyl synthase alpha/beta subunit ( actI-orf1 and -orf2 ), actinorhodin polyketide synthase acyl carrier protein ( actI-orf3 ), and actinorhodin polyketide synthase bifunctional cyclase/dehydrogenase ( actVII ) [ 12 - 14 ] were also highly upregulated: over 5 fold increased expression compared to that in PC (control). Besides these genes in actinorhodin gene cluster, ActVI-ORF1 and ActVI-ORF3 believed to be responsible for pyran ring closure leading to the formation of the benzoisochromanequinone (BIQ) chromophore [ 15 - 17 ] were upregulated.…”

Activation of Microbial Silent Gene Clusters: Genomics Driven Drug Discovery Approaches

“…Identifying these activator signals opens up a platform to activate BGC by switching the regulator to its active state. LysR-Type Transcriptional Regulator (LTTR) genes are found to be present in several BGCs characterized to date [35,36]. These regulators bind to the promoter and activate gene expression in the presence of a co-inducer.…”

Identification of truncated form of NosP as a transcription factor to regulate the biosynthesis of nosiheptide

“…In contrast to global and pleiotropic regulators, the pathway-specific regulators generally control the biosynthesis of a specific secondary metabolite, and their genes are frequently clustered with other functional genes (8). Based on structures and roles, the pathway-specific regulators have been divided into different families, including large ATP-binding regulators of the LuxR family (9,10), LysR-like regulators (11), and the Streptomyces antibiotic regulatory protein (SARP) family (12).…”