title: Microbial transformation of trichostatin A to 2,3-dihydrotrichostatin A.
abstract: A new reduced hydroxamate, 2,3-dihydrotrichostatin A, was created from trichostatin A by employing a recombinant strain of Streptomyces venezuelae as a microbial catalyst. Compared with trichostatin A, 2,3-dihydrotrichostatin A showed similar antifungal activity against Saccharomyces cerevisiae, but, interestingly, approximately twice the cytostatic activity against human small-cell lung cancer cells. The production of 2,3-dihydrotrichostatin A via microbial biotransformation demonstrates that the regiospecific and substrate-flexible hydrogenation by S. venezuelae provides a new approach for creating natural product analogues with improved bioactive properties.
authors.affiliation: Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Chungnam 336-708, Republic of Korea.
authors.forename: Je Won
authors.initials: JW
authors.lastname: Park
authors.forename: Sung Ryeol
authors.initials: SR
authors.lastname: Park
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Han
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Ban
authors.forename: Young Ji
authors.initials: YJ
authors.lastname: Yoo
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.forename: Yeo Joon
authors.initials: YJ
authors.lastname: Yoon
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005818:Genetic Engineering; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C560170:2,3-dihydrotrichostatin A; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001688:Biological Products; D006877:Hydroxamic Acids; C012589:trichostatin A