Biosynthetic studies of omega-cycloheptyl fatty acids in Alicyclobacillus cycloheptanicus. Formation of cycloheptanecarboxylic acid from phenylacetic acid

The formation of the structurally novel, mono-substituted cycloheptane ring in omega-cycloheptyl fatty acids in Alicyclobacillus cycloheptanicus (formerly Bacillus cycloheptanicus) has been examined. Feeding experiments with C-13- and H-2-labeled intermediates demonstrated that cycloheptanecarboxylic acid (3), probably as its CoA thioester, is the starter unit for omega-cycloheptyl fatty acid biosynthesis. Analysis of the resultant labeling pattern from a feeding experiment with [U-C-13(6)]-glucose suggested a shikimate pathway origin of 3 via aromatic amino acids. [1,2-C-13(2)]Phenylacetic acid (6) was efficiently metabolized into the 3-derived moiety in a manner reminiscent of the seven-membered ring Pseudomonas metabolite thiotropocin. The fates of the aromatic and benzylic hydrogens of 6 were determined; these dictated various boundary conditions for the biosynthetic pathway from 6 to 3. Taken together with the results from feeding experiments with postulated cycloheptenylcarboxylate biosynthetic intermediates, the data lead us to propose a pathway which involves an oxidative ring-expansion of 6 to a hydroxynorcaradiene intermediate followed by a series of double bond reductions and dehydrations to the saturated 3.