COMPARISON OF 2 UNUSUAL ENOYL-COA REDUCTASES IN STREPTOMYCES-COLLINUS

Ansatrienin [1], an antifungal antibiotic isolated from Streptomyces collinus, is unusual in that it contains a cyclohexanecarboxylic acid moiety that is derived from shikimic acid. An enoyl CoA reductase catalyzing the conversion of 1-cyclohexenylcarbonyl CoA to cyclohexylcarbonyl CoA reductase was purified to homogeneity, and it is suggested that this enzyme catalyzes the final step in the pathway from shikimic acid to cyclohexanecarboxylic acid. An enzyme catalyzing the conversion of crotonoyl CoA to butyryl CoA was also purified to homogeneity. The stereochemical course of the reactions catalyzed by these two enoyl CoA reductases, together with their physical properties, is discussed in the light of an evolutionary relationship. Evidence of a DELTA2,DELTA3-enoyl-CoA isomerase catalyzing the conversion of 2-cyclohexenylcarbonyl CoA to 1-cyclohexenylcarbonyl CoA has been obtained. Results of mechanistic studies with this enzyme, which is also thought to be involved in the pathway to cyclohexanecarboxylic acid, are shown to be consistent with a preference for the 1S isomer of the substrate and a mechanism of a 1,3-suprafacial shift of a hydrogen catalyzed by a single base at the active site.