Investigations on the biosynthesis of the angucycline group antibiotics aquayamycin and the urdamycins A and B. Results from the structural analysis of novel blocked mutant products

Abstract

In order to investigate mid and early biosynthetic steps of angucycline group antibiotics, approximately 400 mutants of the urdamycin producer Streptomyces fradiae (strain Tii 2717) were prepared, of which ca. 10 76 were selected for further investigations. The selection criterion, i.e., the consideration of only pale-colored metabolite-producing blocked mutants, yielded several mutants whose block was in close proximity to the known late-stage biosynthetic steps. The product patterns were characterized by TLC and HPLC methods, and the structures of five new and one known (but previously not detectable) metabolites were elucidated (3)(4)(5)(6)(7)(8). Their roles in the biosynthetic pathway leading to aquayamycin (1) and on to the urdamycins A (2) and B (9) are proposed. The glycosylation sequence of the urdamycin group and two additional earlier biosynthetic steps leading to aquayamycin (l), the most important angucyclinone, were established in this way.

Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae Tü2717 This paper is dedicated to Professor Heinz Floss, a pioneer in the field of antibiotics, on the occasion of his 65th birthday. The GenBank accession numbers for the sequences reported in this paper are AF164960 and AF164961.

“…Rabelomycin has also been obtained after disruption of Orf6 from S. venezuelae involved in jadomycin biosynthesis. Thus, early steps in the biosynthetic pathways to urdamycin A and jadomycin are identical, and rabelomycin seems to be a central intermediate in both pathways (Yang et al, 1996 ;Rohr et al, 1993 ;Ku$ nzel et al, 1999).…”

“…As aquayamycin is a central intermediate in urdamycin A biosynthesis, attachment of a -olivose moiety at position C-9 should precede the addition of -rhodinose at position C-12b (Rohr et al, 1993). The conclusion that urdGT2 encodes a glycosyltransferase was first based upon sequence similarities between its product and authentic bacterial glycosyltransferases including GraOrf14 and LanGT2.…”

“…The structures of urdamycin I, urdamycin J and urdamycin K were elucidated using NMR spectroscopic methods as well as mass spectrometry (Ku$ nzel et al, 1999). Rabelomycin, the principal product of the urdM deletion mutant of S. fradiae Tu$ 2717 (see above) was identified by its "H NMR spectrum (Rohr et al, 1993), and by electrospray mass spectrometry (m\z 338).…”

Angucyclines: Total syntheses, new structures, and biosynthetic studies of an emerging new class of antibiotics

“…The structure of kanglemycin G (224) [164] was elucidated from spectroscopic and x-ray analysis data. No biological activity data were given.…”

Cloning and characterization of a polyketide synthase gene from Streptomyces fradiae Tü2717, which carries the genes for biosynthesis of the angucycline antibiotic urdamycin A and a gene probably involved in its oxygenation

“…were maintained on 1% malt extract-0.4% yeast extract-0.4% glucose-1 mM CaCl 2 , pH 7.2 (HA medium). Production of urdamycin was in 2% soybean meal-2% glucose, pH 7.2 (AM medium) (41). For the preparation of protoplasts S. fradiae Tü2717 was grown in liquid R2YE for 30 h following the standard procedure (25).…”