Drug Designing: Open Access
Open Access
ISSN: 2169-0138
+44 1223 790975
ISSN: 2169-0138
+44 1223 790975
Carmen Bekeov�?�?�?¡, Mingyar E, Novakova R, Feckova L and Kormanec J
Posters-Accepted Abstracts: Drug Des
Streptomyces are soil Gram-positive bacteria which are characterized by extensive production of biologically active secondary
metabolites, including many antibiotics. We identified angucycline antibiotic auricin in Streptomyces aureofaciens CCM3239.
Auricin is unique angucycline antibiotic containing deoxyaminohexose D-forosamine. Gene cluster aur1 responsible for the
biosynthesis of auricin is localized on the large linear plasmid pSA3239. Auricin is produced in a short time period and its
production is tightly regulated through γ-butyrolactone system, positive regulator aur1P (belongs to OmpR family of response
regulators), negative regulator aur1R (belongs to TetR family of regulators), and at least two SARP (Streptomyces Antibiotic
Regulatory Proteins) regulators. Auricin is glycosylated with the D-forosamine. This sugar moiety is synthesized by the enzymes
encoded by aur1TQSV genes, and other genes as sa59 (a homologue of NDP-hexose aminotransferase) and sa52 (homologue
of NDP-aminohexose N-dimethyltransferase). Attachment of D-forosamine moiety on polyketide scaffold is catalysed by two
close glycosyl tranferases, encoded by genes sa46 and sa53. Mutant strain in both sa46 and sa53 genes produced deglycosylated
aglycon. Deletion analysis of genes in aur1 cluster revealed also other genes involved in the tailoring modification of auricin
molecule. Analysis of the expression of the tailoring genes revealed that they are directly regulated by both SARP family
regulators, Aur1PR3 and Aur1PR4. Therefore the process of auricin regulation is composed of two steps. In the first one, the
gene essential for the core auricin aglycon are directly regulated by Aur1P and Aur1R. In the second step, auricin tailoring genes
are regulated by two SARP regulators, Aur1PR3 and Aur1PR4.