Biotransformation of natural compounds: Unexpected thio conjugation of Sch-642305 with 3-mercaptolactate catalyzed by Aspergillus niger ATCC 16404 cells

Abstract Sch-642305 is produced by the endophytic fungi Phomopsis sp. CMU-LMA and exhibits both antimicrobial and cytotoxic activities. The incubation of Sch-642305 with Aspergillus niger ATCC 16404 resting cells leads to two unexpected thio conjugates. Compound ( 1 ) is formed by the addition of the cysteine metabolite 3-mercaptolactate to the double bond of Sch-642305. Compound ( 1 ) undergoes an intramolecular rearrangement to give compound ( 2 ), which contains two rings: a five-membered hydroxylactone ring and a five-membered thiophene ring. The absolute configuration of compound ( 1 ) is similar to that of the parent compound, but the configuration of the mercaptolactate side-chain was not determined. The absolute configuration of compound ( 2 ) was deduced from the crystal structure and confirmed by the anomal effect of the sulfur atom. To the best of our knowledge, this is the first time such a conjugation rearrangement reactions were observed. The biological significance and the reaction mechanisms are discussed. Compound ( 1 ) exhibits a weak antimicrobial activity against Gram-positive bacteria, whereas derivatives ( 1 ) and ( 2 ) showed an IC 50 of 1 and 1.2 μM, respectively, against colonic epithelial cancer cells.