The biosynthesis of antibiotic A23187

Abstract

The biosynthesis of antibiotic A23187 (I) by S. chartreusis was examined using 14C and 13C labeled substrates in conjunction with chemical degradation and 13C NMR. It has been demonstrated that the three district structural units of the antibiotic are derived from proline (the α-ketopyrrole unit), propionate/acetate (diox-aspiro(5,5)undecane ring), glucose metabolism via a shikimate-type pathway (C 7N 2 or diaminobenzyl unit), and the S-methyl group of methionine (methyl amino of the C 7N 2 unit). Unlike antibiotics that contain a C 7N 1 unit, shikimic acid [ 14C] was incorporated efficiently into the antibiotic and apparently specifically into the C 7N 2 unit. The incorporation of D-glucose[1- 13C], [6- 13C] and [U- 13C 6] is also consistent with a shikimate-type pathway to this unit. None of the aromatic compounds tested were incorporated into the C 7N 2 unit, suggesting that the introduction of the nitrogen functionalities in this moiety occurs before or concommitently with aromization of the six membered carbocyclic ring. These results are in accord with the involvement of a unique biosynthetic pathway in the formation of A23187.