Studies of precursor-directed biosynthesis with streptomyces. Part 2. New and unusual manumycin analogues produced by Streptomyces parvulus

Abstract

The application of a new type of precursor-directed biosynthesis, in which artificial aromatic starter molecules were fed to the manumycin producer Streptomyces parvulus, resulted in new and unusual manumycin analogues for which structures are reported. The new compounds can be divided into three classes; the artificial starter molecule elongated (i) with the triene chain including the C₅N moiety, (ii) with the chiral manumycin C₁₃-side chain only, and (iii) with both substituents. Based on these results it is plausible to differentiate between an amidase linking the chiral C₁₃-side chain to the artificial precursor, and a CoA-transferase activating the aromatic carboxy group for further elongation via the polyketide pathway. The specificity of the enzymes involved with regard to the structure of the aromatic precursor is discussed.