Biosynthesis of Resorcylic Acid Lactone Lasiodiplodin in Lasiodiplodia theobromae

The biosynthesis of lasiodiplodin (1) and its (5S)-5-hydroxylated derivative (2) were investigated by the administration of 13 C-labeled acetates to Lasiodiplodia theobromae. The labeling patterns of biosynthetically C-13-labeled I and 2 were determined by C-13-NMR and INADEQUATE spectra, demonstrating the octaketide origins of I and 2. Taking into account the biosynthetic study of resorcylic acid lactones, the involvement of highly reduced acyl intermediates in the biosynthesis of lasiodiplodins was presumed; thus, we synthesized H-2-labeled hypothetical acyl intermediates of 1, 9-hydroxydecanoic acid (4) and its N-acetylcysteamine thioester (SNALC, 5). When L. theobromae was incubated with 5 mM of a H-2-labeled intermediate, the 2 H-label from the intermediate was incorporated at the expected position of 1. These incorporation studies revealed that 1 was produced via a pathway which closely resembles that of resorcylic acid lactone biosynthesis.