title: Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone.
abstract: Combinatorial biocatalysis was applied to generate a diverse set of dihydroxymethylzearalenone analogs with modified ring structure. In one representative chemoenzymatic reaction sequence, dihydroxymethylzearalenone was first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that creates two new carboxylic groups on the molecule. These groups served as reaction sites for further derivatization involving biocatalytic ring closure reactions with structurally diverse bifunctional reagents, including different diols and diamines. As a result, a library of cyclic bislactones and bislactams was created, with modified ring structures covering chemical space and structure activity relationships unattainable by conventional synthetic means.
authors.affiliation: Department of Metabolism and Biotransformations, AMRI, Albany, NY 12212, USA. joseph.rich@ars.usda.gov
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Rich
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Budde
authors.forename: Luke D
authors.initials: LD
authors.lastname: McConeghey
authors.forename: Ian C
authors.initials: IC
authors.lastname: Cotterill
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Mozhaev
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
authors.forename: Michael A
authors.initials: MA
authors.lastname: Goetz
authors.forename: Annie
authors.initials: A
authors.lastname: Zhao
authors.forename: Peter C
authors.initials: PC
authors.lastname: Michels
authors.forename: Yuri L
authors.initials: YL
authors.lastname: Khmelnitsky
mesh_terms: D055162:Biocatalysis; D015195:Drug Design; D004798:Enzymes / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D013329:Structure-Activity Relationship; D015025:Zearalenone / Q000096:biosynthesis / Q000737:chemistry*
chemical_list: D004798:Enzymes; D015025:Zearalenone; D008049:Lipase