Biosynthetic studies on antibiotic A47934

Abstract

A47934, a peptide antibiotic produced by Streptomyces toyocaensis, belongs to the glycopeptide class of compounds which includes ristocetin and vancomycin. Incorporation studies with radioisotope-labeled substrates indicated that tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylate, acetate, and sulfate were efficiently incorporated into A47934. This is consistent with the reported biosynthesis of other glycopeptide antibiotics. Prototrophic mutants blocked in antibiotic biosynthesis were isolated at a low frequency (0.4%) after mutagenesis. Secretor-convertor pairings of the 36 mutants obtained demonstrated that they belonged to three classes: two groups of secretor-convertor pairs and a larger group of mutants that did not make antibiotic under any condition tested. Neither the secretor-convertor studies not supplementation of the cultures with putative biosynthetic intermediates was useful in identifying the location of the biosynthetic blocks. All studies to determine the timing of the sulfate addition step in the biosynthesis indicated that the sulfate is added prior to the formation of intermediates that possess antimicrobial activity.

Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters

“…toyocaensis A47934 produces the non-glycosylated "glycopeptide" A47934 which comprises the sulfated core heptapeptide of teicoplanin [27,130]. Because A47934 contains no sugar residues, it is a convenient starting scaVold for the addition of sugar residues to generate novel glycopeptides.…”

Vancomycin Assembly: Nature's Way

“…Early structural studies in vancomycin family members showed that all of the Hpg groups in the mature antibiotics were in the D configuration 68. Feeding studies also showed that radiolabeled racemic Hpg may serve as monomers for incorporation into the final glycopeptide 69–71. Feeding experiments with 13 C‐labeled tyrosine demonstrated that the aromatic ring of Hpg was derived from the aromatic ring of tyrosine and the α‐carbon atom of tyrosine forms the carboxylic acid carbon atom of Hpg (Scheme ) 69.…”

Identification of an l -dopa decarboxylase gene from Sorangium cellulosum So ce90

“…In plants, tyrosine, Ldopa, or tryptophan decarboxylases represent a branching point from primary metabolism into secondary metabolic pathways, forming, for example, isoquinoline alkaloids (Kutchan and Zenk 1993;Facchini and De Luca 1994;). In various bacteria, tyrosine, the precursor of L-dopa, and also L-dopa itself, serve also as precursors for the biosynthesis of several antibiotics, such as antibiotic A47934 (Zmijewski et al 1987), lincomycin (Neusser et al 1998) and saframycin (Mikami et al 1985). The close proximity to PKS (ca.…”