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 cycloheptan icus (formerly Bacillus cycloheptanicus) has been examined. Feeding ex periments with C-13- and H-2-labeled intermediates demonstrated that c ycloheptanecarboxylic acid (3), probably as its CoA thioester, is the starter unit for omega-cycloheptyl fatty acid biosynthesis. Analysis o f the resultant labeling pattern from a feeding experiment with [U-C-1 3(6)]-glucose suggested a shikimate pathway origin of 3 via aromatic a mino acids. [1,2-C-13(2)]Phenylacetic acid (6) was efficiently metabol ized into the 3-derived moiety in a manner reminiscent of the seven-me mbered ring Pseudomonas metabolite thiotropocin. The fates of the arom atic and benzylic hydrogens of 6 were determined; these dictated vario us boundary conditions for the biosynthetic pathway from 6 to 3. Taken together with the results from feeding experiments with postulated cy cloheptenylcarboxylate 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.