Crotonyl Coenzyme A Reductase Activity of Bovine Mammary Fatty Acid Synthetase

Beyond ethylmalonyl-CoA: The functional role of crotonyl-CoAcarboxylase/reductase homologs in expanding polyketide diversity

“…14 The authors determined that the purified enzyme shared identical properties to the rat liver reductase reported by Langdon, which was also shown to reduce benzylidene actetone. 14 Over the next 30 years, NADPH-dependent enoyl reductase activity was reported in other mammals, 15 protists, 16 and bacteria 17 before Reynolds and coworkers cloned and overexpressed the first bona fide CCR from Streptomyces collinus. In vitro characterization of the enzyme showed that the homodimeric S. collinus CCR catalyzed the final step in butyryl-CoA formation and was unable to accept any additional enoyl-CoA substrates or NADH as the electron donor.…”

“…JS360. 55 While the Soce-thuggacins and cinnabaramides strictly maintain hexyl side chains in their polyketide structures, the reveromycin family (60-63) of osteoclast-targeting polyketides contains four natural C18 variants suggestive of a mixture of alkylmalonyl-CoA precursors (12)(13)(14)(15). 73,76,77 Though the current biosynthetic literature by Osada and coworkers is focused on reveromycin's novel spiroketal formation, 58 an equally fascinating feature involves the incorporation of four rare or unique PKS extender units in a single position on their structures.…”

“…6). Related branched-chain extender units, such as the proposed 2-methyl-butyrylmalonyl-CoA ( 73) and isopentylmalonyl-CoA (15), may be synthesized in a similar FabHbased fashion to give polyoxypeptin A (74) 85 and reveromycin C (61), 58 respectively. In the case of 61, a FabH-like KS, revR, and CoA-ligase, revS, are located directly upstream of the reveromycin CCR, revT.…”

“…In the case of 61, a FabH-like KS, revR, and CoA-ligase, revS, are located directly upstream of the reveromycin CCR, revT. Similar to 65-72, this three gene cassette is proposed to function in the biosynthesis of the unusual extender units of the reveromycins (12)(13)(14)(15). 58 4 Engineering new polyketides utilizing pathway specific CCR homologs…”

“…In 2009, a new paradigm for polyketide diversification emerged involving the biosynthesis of non-traditional CoAlinked PKS extender units by the reductive carboxylation of a,bunsaturated acyl-CoA precursors by crotonyl-CoA carboxylase/ reductase (CCR) homologs. 6,7 This general mechanism for the biosynthesis of atypical PKS extender units (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) has more than doubled the list of defined CoA-linked precursors incorporated into polyketide structures (Fig. 2).…”