In vivo trapping of polyketide intermediates from an assembly line synthase using malonyl carba(dethia)-N-acetyl cysteamines

摘要

Early-stage intermediates in the biosynthesis of erythromycin A by Saccharopolyspora erythraea were intercepted by malonyl carba(dethia)-N-acetyI cysteamines, generated in vivo from the hydrolysis of the corresponding methyl esters. Polyketide natural products still constitute one of the major sources of medicinal compounds.1 The elucidation of their biosynthesis is thus of the utmost importance for biosynthetic engineering of both plants and microorganisms and for new drug development.2 However the isolation and identification of intermediate species represents a significant obstacle, as they remain covalently tethered to their biosynthetic enzymes, the polyketide synthase multienzymes (PKSs), throughout the assembly of the natural product (Scheme l(a)).