Genetic manipulation of pathway regulation for overproduction of angucycline-like antibiotic auricin in Streptomyces aureofaciens CCM 3239

Abstract

The polyketide gene cluster aur1 is responsible for the production of the antibiotic auricin in Streptomyces aureofaciens CCM 3239. Auricin production is low and strictly regulated by two regulators, Aur1P and Aur1R. To improve auricin yield, we genetically manipulated S. aureofaciens CCM 3239 strain to overcome this strict regulation. A regulatory region including aur1R, aur1P, aur1O and the target biosynthetic aur1Ap promoter were replaced by the strong constitutive ermEp* promoter. However, auricin production was decreased in such a genetically manipulated strain. In the second strategy we placed the aur1P gene for auricin pathway-specific activator under the control of the ermEp* promoter. The resulting strain has been shown to produce 2.8-fold higher amount of auricin compared with the WT strain.

A gene determining a new member of the SARP family contributes to transcription of genes for the synthesis of the angucycline polyketide auricin inStreptomyces aureofaciensCCM 3239

“…We previously characterized the aur1Ap promoter that directed expression of 22 structural genes ( aur1A‐aur1U ) of the auricin cluster (Novakova et al ., , ).…”

“…These results suggest that aur1PR4 has an important role in the positive regulation of auricin biosynthesis. We previously characterized the aur1Ap promoter that directed expression of 22 structural genes (aur1A-aur1U) of the auricin cluster (Novakova et al, 2005(Novakova et al, , 2011a.…”

“…Therefore, along with Aur1PR3, Aur1PR4 constitutes an additional auricin pathway‐specific activator of the SARP family. However, in contrast to aur1PR3 , deletion of aur1PR4 does not substantially affect transcription of the biosynthetic promoter aur1Ap , which controls the expression of 22 auricin biosynthetic genes in the aur1 operon (Novakova et al ., , ). However, a single promoter, sa13p , located upstream of a putative operon of four genes, sa13 , sa12 , sa11 , sa10 (Fig.…”

Production of a Novel Amide‐Containing Polyene by Activating a Cryptic Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08

“…Forced expression of transcriptional activators is a useful approach in genome mining studies, but it has been used mainly to activate specific biosynthetic gene clusters or to improve the production of a specific metabolite . For example, Bergmann et al.…”

Approaches of Genetic Regulation in Actinomycetes for Antibiotic Synthesis

“…With the appearance of drug-resistance bacteria, many researches today are focusing on how to improve the biosynthesis of antibiotic in actinomycetes and how to exploit new antibiotics [3]. However, the most effective way to achieve this is by regulating the process of secondary metabolism in genetic levels [4,5]. Therefore, this overview will summarize current approaches of genetic regulation in the antibiotic synthesis of actinomycetes.…”