No abstract

The incorporation of ethyl [I ,2,3,4-13C& and ethyl [I ,3-13C2]-acetoacetate into nonactic acid in cultures of Streptomyces griseus revealed the incorporation of several C2 units derived from acetyl-CoA, as well as a single intact C3 unit at C(l)-C(2)-C(lO).The carbon skeleton of nonactin (1) is assembled in Streptomyces griseus from two units of acetyl-CoA, one of succinyl-CoA, and one of propionyl-CoA, as revealed by 13C labelling experiments.1J The familiar concept of a 'starter unit' is, however, obscure in this case because of the unusual role of succinate as a precursor of the complete tetrahydrofuran ring in each nonactic acid subunit2 (see Scheme 1). Thus chain assembly could be initiated with acetyl-CoA, or with succinyl-CoA. We decided to investigate the order in which the building blocks are assembled and focussed initially on the possibility that two units of acetyl-CoA might be combined to afford acetoacetyl-CoA. This C4 unit could then combine with succinyl-Co A in a process involving an overall decarboxylative condensation. Finally, methylmalonyl-CoA might be