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

The origin of all oxygen atoms of the structurally unique polyketide antibi otic kendomycin 1 was confirmed by feeding [1-C-13,O-18(2)]acetate, [1-C-13 ,O-18(2)]propionate and O-18(2) to Streptomyces violaceoruber (strain 3844- 33C) resulting in a more detailed insight into the biosynthesis of 1. Furth er information about the biosynthesis of the starter unit in which a chalco ne synthase (CHS) must be involved was obtained from comparison of recent l iterature data with the requirements of the kendomycin biosynthesis. The in corporation of acetate into the methylmalonyl extender units reported previ ously was investigated by additional feeding [2-C-13]malonic acid and [1,4- C-13(2)]succinic acid to the strain. As a result, the coexistence of two in dependent pathways to methylmalonyl-CoA was demonstrated. Furthermore, feed ing of N-acetylcysteamine and other thiols resulted in the formation of the new kendomycin derivatives 2 and 3 in good yields.