Biosynthetic studies on the xanthone antibiotics lysolipins X and I

Abstract

Feeding experiments with 13 C and 18 O-labeled precursors revealed that the polycyclic xanthone antibiotics, the lysolipins X (1) and I (2), is derived from the polyketide pathway (12 malonate units), the C 1 pool (methionine), molecular oxygen, and the nitrogen pool. Surprisingly, an intact malonate moiety serves as the three-carbon starter unit of the polyketide backbone, and 9 of the 12 oxygen atoms of I originate from molecular oxygen, including both of the xanthone oxygen atoms. The orientation of the malonate unit incorporated intact into lysolipin is unique and opposite from those in tetracycline and cycloheximide, i.e., the activated carbon of malonyl CoA is bound to the nitrogen of the lysolipin isoquinoline ring and the CO 2 -derived carbon serves as the starter of the polyketide chain