Migrastatin and Dorrigocins Are Shunt Metabolites of Iso-Migrastatin

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Abstract
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.