Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone.
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.
Rich
Joseph O
JO
Department of Metabolism and Biotransformations, AMRI, Albany, NY 12212, USA. joseph.rich@ars.usda.gov
Budde
Cheryl L
CL
McConeghey
Luke D
LD
Cotterill
Ian C
IC
Mozhaev
Vadim V
VV
Singh
Sheo B
SB
Goetz
Michael A
MA
Zhao
Annie
A
Michels
Peter C
PC
Khmelnitsky
Yuri L
YL
D055162:Biocatalysis; D015195:Drug Design; D004798:Enzymes / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D013329:Structure-Activity Relationship; D015025:Zearalenone / Q000096:biosynthesis / Q000737:chemistry*
D004798:Enzymes; D015025:Zearalenone; D008049:Lipase