Biooxidation of bridged cycloketones using Baeyer-Villiger monooxygenases of various bacterial origin.
Bridged cycloketones were synthesized and utilized as substrates to study biooxidations mediated by Baeyer-Villiger monooxygenases (BVMO) of various bacterial origin. The required enzymes were heterologously produced by recombinant overexpression systems based on Escherichia coli to enable facile recycling of the required nicotinamide cofactors during the whole-cell biotransformations. Ketone precursors of various structural demands were chosen to evaluate steric limitations and flexibility of the active site of BVMOs. By desymmetrization of the prochiral substrates, four to six stereogenic centers were generated within a single biooxidation step. The enzyme library investigated in this study allowed access to antipodal lactone products with excellent enantioselectivity in several cases. Together with a distinct substrate acceptance profile, the recently proposed classification into two groups of cycloketone converting BVMOs was supported by the biotransformation results obtained within this study.
Snajdrova
Radka
R
Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, A-1060 Vienna, Austria.
Braun
Ingbert
I
Bach
Thorsten
T
Mereiter
Kurt
K
Mihovilovic
Marko D
MD
D001419:Bacteria / Q000201:enzymology* / Q000235:genetics; D002384:Catalysis; D003500:Cyclization; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D019151:Peptide Library; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
D007659:Ketones; D019151:Peptide Library; D011994:Recombinant Proteins; D006899:Mixed Function Oxygenases