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The devil is in the details: The chemical basis and mechanistic versatility of flavoprotein monooxygenases
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2020-12-24 , DOI: 10.1016/j.abb.2020.108732
Marina Toplak 1 , Arne Matthews 1 , Robin Teufel 1
Affiliation  

The ubiquitous flavoenzymes commonly catalyze redox chemistry such as the monooxygenation of organic substrates and are both widely utilized in nature (e.g., in primary and secondary metabolism) and of significant industrial interest. In this work, we highlight the structural and mechanistic characteristics of the distinct types of flavoprotein monooxygenases (FPMOs). We thereby illustrate the chemical basis of FPMO catalysis, which enables reactions such as (aromatic) hydroxylation, epoxidation, (de)halogenation, heteroatom oxygenation, Baeyer-Villiger oxidation, α-hydroxylation of ketones, or non-oxidative carbon-hetero bond cleavage. This seemingly unmatched versatility in oxygenation chemistry results from extensive fine-tuning and regiospecific functionalization of the flavin cofactor that is tightly controlled by the surrounding protein matrix. Accordingly, FPMOs steer the formation of covalent flavin-oxygen adducts for oxygen transfer in the form of the classical flavin-C4a-(hydro)peroxide or the recently discovered N5-functionalized flavins (i.e. the flavin-N5-oxide and the flavin-N5-peroxide), while in rare cases covalent oxygen adduct formation may be foregone entirely. Finally, we speculate about hitherto undiscovered flavin-mediated oxygenation reactions and compare FPMOs to cytochrome P450 monooxygenases, before addressing open questions and challenges for the future investigation of FPMOs.



中文翻译:

魔鬼在细节中:黄素蛋白单加氧酶的化学基础和机制多功能性

普遍存在的黄素酶通常催化氧化还原化学,例如有机底物的单氧化,并且在自然界中广泛使用(例如,在初级和次级代谢中)并且具有重要的工业意义。在这项工作中,我们强调了不同类型的黄素蛋白单加氧酶 (FPMO) 的结构和机制特征。因此,我们说明了 FPMO 催化的化学基础,它能够进行诸如(芳族)羟基化、环氧化、(脱)卤化、杂原子氧化、Baeyer-Villiger 氧化、酮的α-羟基化或非氧化性碳-杂键断裂等反应. 这种氧化化学中看似无与伦比的多功能性是由受周围蛋白质基质严格控制的黄素辅因子的广泛微调和区域特异性功能化造成的。因此,FPMO 以经典的黄素-C4a-(氢)过氧化物或最近发现的 N5 功能化黄素(即黄素-N5-氧化物和黄素-N5)的形式引导形成共价黄素-氧加合物以进行氧转移。 -过氧化物),而在极少数情况下,可能会完全避免形成共价氧加合物。最后,我们推测迄今为止尚未发现的黄素介导的氧合反应,并将 FPMO 与细胞色素 P450 单加氧酶进行比较,然后再解决未来对 FPMO 研究的开放性问题和挑战。FPMO 以经典的黄素-C4a-(氢)过氧化物或最近发现的 N5 功能化黄素(即黄素-N5-氧化物和黄素-N5-过氧化物)的形式引导形成共价黄素-氧加合物以进行氧转移),而在极少数情况下,可能会完全避免形成共价氧加合物。最后,我们推测迄今为止尚未发现的黄素介导的氧合反应,并将 FPMO 与细胞色素 P450 单加氧酶进行比较,然后再解决未来对 FPMO 研究的开放性问题和挑战。FPMO 以经典的黄素-C4a-(氢)过氧化物或最近发现的 N5 功能化黄素(即黄素-N5-氧化物和黄素-N5-过氧化物)的形式引导形成共价黄素-氧加合物以进行氧转移),而在极少数情况下,可能会完全避免形成共价氧加合物。最后,我们推测迄今为止尚未发现的黄素介导的氧合反应,并将 FPMO 与细胞色素 P450 单加氧酶进行比较,然后再解决未来对 FPMO 研究的开放性问题和挑战。

更新日期:2020-12-25
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