LAUSR

The conversion of shikimate to cyclohexanecarboxyl-CoA (CHC-CoA) involves an exquisite orchestra of multiple enzymes to proceed stereospecifically and avoid aromaticity, but little is known regarding the details of this intriguing enzymatic reaction cascade. Through both in vitro and in vivo analysis, we provide a plausible enzymatic pathway for CHC-CoA biosynthesis from shikimate. This pathway highlights a shikimoyl-CoA synthetase that is highly promiscuous toward a wide range of cycloalkane and benzoate substrates. In addition, an acyl-CoA dehydrogenase is shown to have evolved to be a FAD-dependent nonredox dehydratase that is distinct from any known FAD-dependent dehydratases.