Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
J Ind Microbiol Biotechnol. 2021 Jun 4;48(3-4). doi: 10.1093/jimb/kuab021.
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.
自由基环化反应是次生代谢物生物合成和具有社会价值分子的化学合成中的关键反应。在这篇综述中，我们强调了生物催化自由基环化反应中使用的一般机制。我们特别强调了参与麦考环素和万古霉素生物合成的细胞色素 P450 单加氧酶（P450s）、参与海兔毒素、东莨菪碱和异青霉素 N 生物合成的非血红素铁和α-酮戊二酸依赖性双加氧酶（Fe/αKGDs）以及促进 Oxetanocin A、甲萘醌和 F420 生物合成的自由基 S-腺苷甲硫氨酸（SAM）酶。除了天然机制外，我们还研究了重新利用黄素依赖性“ene”-还原酶（ERED）进行非天然自由基环化反应。总的来说，这些一般机制强调了酶利用自由基机制来增强和增强复杂分子合成的机会。
