Teufel Robin
ZBSA, Center for Biological Systems Analysis, University of Freiburg, 79104 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Arch Biochem Biophys. 2017 Oct 15;632:20-27. doi: 10.1016/j.abb.2017.06.008. Epub 2017 Jun 12.
Natural products are distinct and often highly complex organic molecules that constitute not only an important drug source, but have also pushed the field of organic chemistry by providing intricate targets for total synthesis. How the astonishing structural diversity of natural products is enzymatically generated in biosynthetic pathways remains a challenging research area, which requires detailed and sophisticated approaches to elucidate the underlying catalytic mechanisms. Commonly, the diversification of precursor molecules into distinct natural products relies on the action of pathway-specific tailoring enzymes that catalyze, e.g., acylations, glycosylations, or redox reactions. This review highlights a selection of tailoring enzymes that employ riboflavin (vitamin B2)-derived cofactors (FAD and FMN) to facilitate unusual redox catalysis and steer the formation of complex natural product pharmacophores. Remarkably, several such recently reported flavin-dependent tailoring enzymes expand the classical paradigms of flavin biochemistry leading, e.g., to the discovery of the flavin-N5-oxide - a novel flavin redox state and oxygenating species.
天然产物是独特且往往高度复杂的有机分子，它们不仅是重要的药物来源，还通过提供用于全合成的复杂目标推动了有机化学领域的发展。天然产物惊人的结构多样性是如何在生物合成途径中通过酶促产生的，仍然是一个具有挑战性的研究领域，这需要详细而复杂的方法来阐明潜在的催化机制。通常，前体分子向不同天然产物的多样化依赖于途径特异性修饰酶的作用，这些酶催化例如酰化、糖基化或氧化还原反应。本综述重点介绍了一些利用核黄素（维生素B2）衍生的辅因子（FAD和FMN）来促进异常氧化还原催化并引导复杂天然产物药效团形成的修饰酶。值得注意的是，最近报道的几种此类黄素依赖性修饰酶扩展了黄素生物化学的经典范式，例如导致发现了黄素-N5-氧化物——一种新型的黄素氧化还原状态和氧化物种。
