Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

Abstract

We describe the unprecedented formation of six ansamitocin derivatives that are deoxygenated at C-7 of the ansamitocin core, obtained during fermentation experiments by employing a variety of Actinosynnema pretiosum mutants and mutasynthetic approaches. We suggest that the formation of these derivatives is based on elimination at C-7/C-8 followed by reduction(s) of the intermediate enone. In bioactivity tests, only ansamitocin derivatives bearing an ester side chain at C-3 showed strong antiproliferative activity.

Keywords

• ansamitocins
• antibiotics
• antitumor agents
• mutasynthesis
• natural products