A Complex Signaling Cascade Governs Pristinamycin Biosynthesis in Streptomyces pristinaespiralis.

Pristinamycin production in Streptomyces pristinaespiralis Pr11 is tightly regulated by an interplay between different repressors and activators. A γ-butyrolactone receptor gene (spbR), two TetR repressor genes (papR3 and papR5), three SARP (Streptomyces antibiotic regulatory protein) genes (papR1, papR2, and papR4), and a response regulator gene (papR6) are carried on the large 210-kb pristinamycin biosynthetic gene region of Streptomyces pristinaespiralis Pr11. A detailed investigation of all pristinamycin regulators revealed insight into a complex signaling cascade, which is responsible for the fine-tuned regulation of pristinamycin production in S.

The bifunctional role of aconitase in Streptomyces viridochromogenes Tü494.

In many organisms, aconitases have dual functions; they serve as enzymes in the tricarboxylic acid cycle and as regulators of iron metabolism. In this study we defined the role of the aconitase AcnA in Streptomyces viridochromogenes Tü494, the producer of the herbicide phosphinothricyl-alanyl-alanine, also known as phosphinothricin tripeptide or bialaphos. A mutant in which the aconitase gene acnA was disrupted showed severe defects in morphology and physiology, as it was unable to form any aerial mycelium, spores nor phosphinothricin tripeptide.

Characterization of the 'pristinamycin supercluster' of Streptomyces pristinaespiralis.

Pristinamycin, produced by Streptomyces pristinaespiralis Pr11, is a streptogramin antibiotic consisting of two chemically unrelated compounds, pristinamycin I and pristinamycin II. The semi-synthetic derivatives of these compounds are used in human medicine as therapeutic agents against methicillin-resistant Staphylococcus aureus strains. Only the partial sequence of the pristinamycin biosynthetic gene cluster has been previously reported.

Identification and functional characterization of phenylglycine biosynthetic genes involved in pristinamycin biosynthesis in Streptomyces pristinaespiralis.

Pristinamycin I (PI), a streptogramin type B antibiotic produced by Streptomyces pristinaespiralis, contains the aproteinogenic amino acid L-phenylglycine. Recent sequence analysis led to the identification of a set of putative phenylglycine biosynthetic genes. Successive inactivation of the individual genes resulted in a loss of PI production.

Phosphinothricin-tripeptide biosynthesis: an original version of bacterial secondary metabolism?

Streptomyces viridochromogenes Tü494 produces the herbicide phosphinothricyl-alanyl-alanine (phosphinothricin-tripeptide=PTT; bialaphos). Its bioactive moiety phosphinothricin competitively inhibits bacterial and plant glutamine synthetases. The biosynthesis of PTT includes the synthesis of the unusual amino acid N-acetyl-demethyl-phosphinothricin and a three step condensation via non-ribosomal peptide synthetases.