The shikimic acid pathway and polyketide biosynthesis

The shikimic acid pathway, ubiquitous in microorganisms and plants, provides precursors for the biosynthesis of primary metabolites such as the aromatic amino acids and folic acid, Several branchpoints from the primary metabolic pathway also provide aromatic and, in some unusual cases, nonaromatic precursors for the biosynthesis of secondary metabolites, We report herein recent progress in the analysis of two unusual branches of the shikimic acid pathway in streptomycetes; the formation of the cyclohexanecarboxylic acid (CHC)-derived moiety of the antifungal agent ansatrienin and the dihydroxycyclohexanecarboxylic acid (DHCHC) starter unit for the biosynthesis of the immunosuppressant ascomycin, A gene for 1-cyclohexenylcarbonyl-CoA reductase, chcA, which plays a role in catalyzing three of the reductive steps leading from shikimic acid to CHC has been characterized from Streptomyces collinus, A cluster of six open reading frames (ORFs) has been identified by sequencing in both directions from chcA and the putative role of these in CHC biosynthesis is discussed, The individual steps involved in the biosynthesis of DHCHC from shikimic acid in Streptomyces hygroscopicus var ascomyceticus has been delineated and shown to be stereochemically and enzymatically distinct from the CHC pathway, A dehydroquinate dehydratase gene (dhq) likely involved in providing shikimic acid for both DHCHC biosynthesis and primary metabolism has been cloned, sequenced and characterized.