Effect of stereochemistry of avermectin-like 6,6-spiroketals on biological activities and endogenous biotransformations in Streptomyces avermectinius

Abstract

Natural avermectins (AVEs) share a 6,6-spiroketal moiety with an exclusive R configuration at the C21 spirocyclic junction. Herein, we report the characterization of nine AVE-like spiroketals of two types (C21 S and R) in a mutant strain that lacks spirocyclase activity. Comparative analysis of their structures facilitated evaluation of the effect of stereochemistry on endogenous biotransformations and biological activities of the spiroketals.

Keywords: avermectins; biosynthesis; endogenous biotransformation; spiro compounds; spiroketals.