Biosynthetic Studies on the Xanthone Antibiotics Lysolipins X and I

Feeding experiments with ¹³C and ¹⁸O-labeled precursors revealed that the molecular framework of the polycyclic xanthone antibiotics, the lysolipins X (1) and I (2), is derived from the polyketide pathway (12 malonate units), the C₁ 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 1 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 CO₂-derived carbon serves as the starter of the polyketide chain. From the biogenetic origin of the oxygen atoms several unusual prearomatic deoxygenation steps early in the biosynthesis have to be postulated.