title: 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 IC₅₀ of 1 and 1.2 μM, respectively, against colonic epithelial cancer cells.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique C.N.R.S., Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Adelin
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Martin
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Bricot
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cortial
authors.forename: Pascal
authors.initials: P
authors.lastname: Retailleau
authors.forename: Jamal
authors.initials: J
authors.lastname: Ouazzani
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001234:Aspergillus niger / Q000166:cytology / Q000378:metabolism*; D055162:Biocatalysis; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D018942:Macrolides; C482741:Sch 642305; D013438:Sulfhydryl Compounds; C008361:beta-mercaptolactate