Stereochemical integrity of oxazolone ring-containing jadomycins.
The jadomycins are a series of natural products produced by Streptomyces venzuelae ISP5230 in response to ethanol shock. A unique structural feature of these angucyclines is the oxazolone ring, the formation of which is catalyzed by condensation of a biosynthetic aldehyde intermediate and an amino acid. The feeding of enantiomeric forms of alpha-amino acids indicates that the amino acid is incorporated by S. venezuelae ISP5230 without isomerization at the alpha-carbon. The characterization of the first two six-membered E-ring-containing jadomycins is reported. These precursor-directed biosynthesis studies indicate flexibility in the acceptor substrate specificity of the glycosyltransferase, JadS. Analysis of cytotoxicity data against two human breast cancer cell lines indicates that the nature of the substitution at the alpha-carbon, rather than the stereochemistry, influences biological activity.
Borissow
Charles N
CN
College of Pharmacy, Burbidge Building, Dalhousie University, 5968 College Street, Halifax, Nova Scotia, B3H 3J5, Canada.
Graham
Cathy L
CL
Syvitski
Ray T
RT
Reid
Taryn R
TR
Blay
Jonathan
J
Jakeman
David L
DL
D001943:Breast Neoplasms / Q000628:therapy; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D007532:Isoleucine / Q000737:chemistry; D007546:Isoquinolines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009285:Naphthoquinones / Q000737:chemistry*; D010081:Oxazolone / Q000737:chemistry*; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism
D007546:Isoquinolines; D009285:Naphthoquinones; C506597:jadomycin A; D007532:Isoleucine; C081750:jadomycin B; D010081:Oxazolone; D000431:Ethanol; D002244:Carbon