Two pathways for pyrrole formation in coumermycin A(1) biosynthesis: the central pyrrole moiety is formed from L-threonine.

Coumermycin A(1) is an aminocoumarin antibiotic produced by Streptomyces rishiriensis. It contains three pyrrole rings, that is, two terminal 5-methyl-pyrrole-2-carboxyl moieties and a central 3-methylpyrrole-2,4-dicarboxylic acid moiety. The biosynthesis of the terminal pyrrole moieties has been elucidated previously.

Identification of a napsamycin biosynthesis gene cluster by genome mining.

Napsamycins are potent inhibitors of bacterial translocase I, an essential enzyme in peptidoglycan biosynthesis, and are classified as uridylpeptide antibiotics. They comprise an N-methyl diaminobutyric acid, an ureido group, a methionine and two non-proteinogenic aromatic amino acid residues in a peptide backbone that is linked to a 5'-amino-3'-deoxyuridine by an unusual enamide bond. The napsamycin gene cluster was identified in Streptomyces sp.

Identification and structural elucidation of new caprazamycins from Streptomyces sp. MK730-62F2 by liquid chromatography/electrospray ionization tandem mass spectrometry.

The development of reliable analytic methods, capable of separating mixtures of secondary metabolites as well as providing structural information, is essential for the investigation of secondary metabolites, e.g. from Streptomyces.

Heterologous expression of the biosynthetic gene clusters of coumermycin A(1), clorobiocin and caprazamycins in genetically modified Streptomyces coelicolor strains.

The biosynthetic gene clusters of the aminocoumarin antibiotics clorobiocin and coumermycin A(1) and of the liponucleoside antibiotic caprazamycin were stably integrated into the genomes of different host strains derived from Streptomyces coelicolor A3(2). For the heterologous expression of clorobiocin derivatives in a chemically defined medium, inclusion of 0.6% of the siloxylated ethylene oxide/propylene oxide copolymer Q2-5247 into the growth medium proved to result in a 4.

Formation and attachment of the deoxysugar moiety and assembly of the gene cluster for caprazamycin biosynthesis.

Caprazamycins are antimycobacterials produced by Streptomyces sp. MK730-62F2. Previously, cosmid cpzLK09 was shown to direct the biosynthesis of caprazamycin aglycones, but not of intact caprazamycins.

Reducing the variability of antibiotic production in Streptomyces by cultivation in 24-square deepwell plates.

Highly reproducible production values of the aminocoumarin antibiotic novobiocin were achieved by cultivation of a heterologous Streptomyces producer strain in commercially available square deepwell plates consisting of 24 wells of 3 ml culture volume each. Between parallel cultivation batches in the deepwell plates, novobiocin accumulation showed standard deviations of 4-9%, compared to 39% in baffled Erlenmeyer flasks. Mycelia used as inoculum could be frozen in the presence of 20% peptone and stored at -70 degrees C, allowing repeated cultivations from the same batch of inoculum over extended periods of time.

A new arylsulfate sulfotransferase involved in liponucleoside antibiotic biosynthesis in streptomycetes.

Sulfotransferases are involved in a variety of physiological processes and typically use 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfate donor substrate. In contrast, microbial arylsulfate sulfotransferases (ASSTs) are PAPS-independent and utilize arylsulfates as sulfate donors. Yet, their genuine acceptor substrates are unknown.

Identification and manipulation of the caprazamycin gene cluster lead to new simplified liponucleoside antibiotics and give insights into the biosynthetic pathway.

Caprazamycins are potent anti-mycobacterial liponucleoside antibiotics isolated from Streptomyces sp. MK730-62F2 and belong to the translocase I inhibitor family. Their complex structure is derived from 5'-(beta-O-aminoribosyl)-glycyluridine and comprises a unique N-methyldiazepanone ring.