TY - JOUR
T1 - Activation modes in biocatalytic radical cyclization reactions
AU - Ye, Yuxuan
AU - Fu, Haigen
AU - Hyster, Todd K.
N1 - Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of Society of Industrial Microbiology and Biotechnology.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Radical cyclizations are essential reactions in the biosynthesis of secondary metabolites and the chemical synthesis of societally valuable molecules. In this review, we highlight the general mechanisms utilized in biocatalytic radical cyclizations. We specifically highlight cytochrome P450 monooxygenases (P450s) involved in the biosynthesis of mycocyclosin and vancomycin, nonheme iron- and α-ketoglutarate-dependent dioxygenases (Fe/αKGDs) used in the biosynthesis of kainic acid, scopolamine, and isopenicillin N, and radical S-adenosylmethionine (SAM) enzymes that facilitate the biosynthesis of oxetanocin A, menaquinone, and F420. Beyond natural mechanisms, we also examine repurposed flavin-dependent “ene”-reductases (ERED) for non-natural radical cyclization. Overall, these general mechanisms underscore the opportunity for enzymes to augment and enhance the synthesis of complex molecules using radical mechanisms.
AB - Radical cyclizations are essential reactions in the biosynthesis of secondary metabolites and the chemical synthesis of societally valuable molecules. In this review, we highlight the general mechanisms utilized in biocatalytic radical cyclizations. We specifically highlight cytochrome P450 monooxygenases (P450s) involved in the biosynthesis of mycocyclosin and vancomycin, nonheme iron- and α-ketoglutarate-dependent dioxygenases (Fe/αKGDs) used in the biosynthesis of kainic acid, scopolamine, and isopenicillin N, and radical S-adenosylmethionine (SAM) enzymes that facilitate the biosynthesis of oxetanocin A, menaquinone, and F420. Beyond natural mechanisms, we also examine repurposed flavin-dependent “ene”-reductases (ERED) for non-natural radical cyclization. Overall, these general mechanisms underscore the opportunity for enzymes to augment and enhance the synthesis of complex molecules using radical mechanisms.
KW - Biocatalysis
KW - Natural product synthesis
KW - Photoenzymatic reaction
KW - Radical cyclization
KW - ene-reductase
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U2 - 10.1093/jimb/kuab021
DO - 10.1093/jimb/kuab021
M3 - Article
C2 - 33674826
SN - 1367-5435
VL - 48
JO - Journal of Industrial Microbiology and Biotechnology
JF - Journal of Industrial Microbiology and Biotechnology
IS - 3-4
M1 - kuab021
ER -