Chemistry of bleomycin. XXVI. Biosynthetic study using 13C-enriched precursors.

Copper(I)-bleomycin: structurally unique complex that mediates oxidative DNA strand scission

“…Presently, 'H and 13C NMR spectroscopy of Cu(I)-BLM has been employed to provide additional data concerning the nature of this bleomycin would permit definitive assignments to be made for Cu(I)-BLM complexes if unambiguous assignments of the 13C natural abundance spectra were available. To date, the 13C spectrum of bleomycin has been analyzed on the basis of spectral data derived from an extensive range of derivatives and precursors (Naganawa et al, 1977), which have been augmented by selective biosynthetic incorporation of 13C-labeled precursors (Nakatani et al, 1980). Resonances have been designated on the basis of similarity to spectral data provided by "chemical shift maps" (Naganawa et al, 1977) and values calculated from the presumed structures.…”

Uncatalyzed microwave deuterium exchange labeling of bleomycin A2

“…Stable isotope labeled bleomycin A 2 containing > M þ 3 isotope labeling with no detectable M þ 0 was needed as a mass spectroscopic standard for mouse stratification studies of bleomycin clearance using SNPs prediction. Though bleomycin-labeling methods 2,3 have been described in the literature, these methods require bacterial uptake of labeled unnatural amino acids or other sources of isotopes during fermentation. The bleomycins must then be extracted from the culture, and the desired-labeled bleomycin must be isolated and identified.…”

Hybrid Peptide–Polyketide Natural Products: Biosynthesis and Prospects toward Engineering Novel Molecules

“…On the basis of feeding experiments with isotope-labeled precursors and isolation of biosynthetic intermediates and shunt metabolites, such a model in fact was implicated long before the characterization of the modular structure of either NRPS or PKS. For example, by feeding 14 C-and 13 C-labeled biosynthetic precursors, Fujii, Umezawa, Takita, and coworkers (Fujii, 1979;Nakatani et al, 1980;Takita, 1984;Takita and Muroka, 1990) showed that the aglycone of bleomycin (7) was derived from a Ser, two Asn, a His, an Ala, an acetate, a Thr, a ;-Ala, and two Cys in Streptomyces verticillus ATCC15003, a fact that supports a hybrid peptide polyketide biogenesis. Subsequent isolation and structural determination of a series of biosynthetic intermediates, such as P-3A (18), P-4 (19), and P-6m (20), from fermentation cultures led them to propose the biosynthetic pathway for 7 as shown in Fig.…”