Incorporation of [ 1J3C]-, [2-I3C]-and [ 1,2-13C2]-acetate, [ I-13C]-propionate, [13C-CH,]-~-methionine and [3-'4C]-~~-tryptophan into chaetoglobosin A (1) and 19-0-acetylchaetoglobosin A (2) by Chaetomium globosum demonstrated that the building blocks of 1 and 2 are 9 and 10 units of acetate/malonate respectively, 3 units of methionine and 1 unit of tryptophan. Propionate is incorporated indirectly after several biological transformations. Using [2-I3C, 2-2H,]-acetate as precursor, the starter unit of the polyketide-chain was identified. Experiments which [13C, *H3-CH,]-~-methionine demonstrated that the three C-methylations occur with retention of all three H-atoms of the methyl group. Incorporation experiments with various I4Cand 3H-labelled tryptophan samples and with [2-2H]-and [2-15N]-~-tryptophan showed that the amino acid is incorporated intact with retention of both the a-Hand the a-N-atom. On the basis of these results a more detailed general scheme of the cytochalasan biogenesis is proposed.
Introduction. -Since the isolation and structure elucidation of the first two cytochalasans, cytochalasin A and B [I] in 1966, the number of members of this class of microbial metabolites has risen to 362). Nevertheless, studies on the biosynthesis of cytochalasans have until now been reported only for cytochalasin B [4] [5a], a phenyl-24-oxa-[14]cytochalasan, and cytochalasin D [5a] [6], a phenyl-[ 1 l]cytochalasan. The results of these investigations clearly demonstrate closely related biogenetic pathways from a polyketide-derived chain, with respectively two and three introduced C,-units, and which is combined with phenylalanine. The great structural similarity of the four basic types of cytochalasans known permitted us to postulate a common biogenetic scheme for all the members of this class of metabolites 171. It is evident that to establish the validity of this general biogenetic scheme, additional experimental data are required, such as the isolation of intermediates of the biogenetic I )
2 )
Author to whom correspondence should be addressed. Recent additions to this class of compounds include engleromycin (21, 19-~acetylchaetoglobosin B and D [3a] and cytochalasin K, L and M [3b].