Biosynthesis of kendomycin: origin of the oxygen atoms and further investigations

Abstract

The origin of all oxygen atoms of the structurally unique polyketide antibiotic kendomycin 1 was confirmed by feeding [1-¹³C,¹⁸O₂]acetate, [1-¹³C,¹⁸O₂]propionate and ¹⁸O₂ to Streptomyces violaceoruber (strain 3844-33C) resulting in a more detailed insight into the biosynthesis of 1. Further information about the biosynthesis of the starter unit in which a chalcone synthase (CHS) must be involved was obtained from comparison of recent literature data with the requirements of the kendomycin biosynthesis. The incorporation of acetate into the methylmalonyl extender units reported previously was investigated by additional feeding [2-¹³C]malonic acid and [1,4-¹³C₂]succinic acid to the strain. As a result, the coexistence of two independent pathways to methylmalonyl-CoA was demonstrated. Furthermore, feeding of N-acetylcysteamine and other thiols resulted in the formation of the new kendomycin derivatives 2 and 3 in good yields.