Migrastatin and dorrigocins are shunt metabolites of iso-migrastatin.
Fermentation of Streptomyces platensis NRRL18993 typically accumulated migrastation (1), dorrigocin A (2) and B (3), and 13-epi-dorrigocin A (5). Supplement of XAD-16 resin to the fermentation, in contrast, resulted in exclusive production of iso-migrastatin (4). In vitro studies showed that 1, 2, 3, and 5 are stable in aqueous solution but 4 undergoes rapid conversion into 1, 2, 3, and 5 under the same condition. These results revealed that 4 is the only bona fide natural product biosynthesized by S. platensis, and 1, 2, 3, and 5 are shunt metabolites of 4. This study also established the stereochemistry of 2-5 with the exception of C-11 for 3 and 4. A mechanism for H2O-mediated regio- and stereospecific rearrangement of 4 to 1, 2, 3, and 5 is proposed and supported by incorporation of 18O from H218O.
Ju
Jianhua
J
Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53705, USA.
Lim
Si-Kyu
SK
Jiang
Hui
H
Shen
Ben
B
D002851:Chromatography, High Pressure Liquid; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D010881:Piperidones / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism
D007783:Lactones; D018942:Macrolides; D010881:Piperidones; C089606:dorrigocin A; C455261:isomigrastatin; C418199:migrastatin