Bitchagno Gabin Thierry M, Nchiozem-Ngnitedem Vaderament-A, Melchert Dennis, Fobofou Serge Alain
Agrobiosciences, Mohamed IV Polytechnic University, Ben-Guerir, Morocco.
Plant Sciences and Bioeconomy, Rothamsted Research, Harpenden, UK.
Nat Rev Chem. 2022;6(11):806-822. doi: 10.1038/s41570-022-00431-4. Epub 2022 Oct 14.
Natural products possess structural complexity, diversity and chirality with attractive functions and biological activities that have significantly impacted drug discovery initiatives. Chiral natural products are abundant in nature but rarely occur as racemates. The occurrence of natural products as racemates is very intriguing from a biosynthetic point of view; as enzymes are chiral molecules, enzymatic reactions generating natural products should be stereospecific and lead to single-enantiomer products. Despite several reports in the literature describing racemic mixtures of stereoisomers isolated from natural sources, there has not been a comprehensive review of these intriguing racemic natural products. The discovery of many more natural racemates and their potential enzymatic sources in recent years allows us to describe the distribution and chemical diversity of this 'class of natural products' to enrich discussions on biosynthesis. In this Review, we describe the chemical classes, occurrence and distribution of pairs of enantiomers in nature and provide insights about recent advances in analytical methods used for their characterization. Special emphasis is on the biosynthesis, including plausible enzymatic and non-enzymatic formation of natural racemates, and their pharmacological significance.
天然产物具有结构复杂性、多样性和手性，以及吸引人的功能和生物活性，这些对药物发现计划产生了重大影响。手性天然产物在自然界中很丰富，但很少以外消旋体的形式出现。从生物合成的角度来看，天然产物以外消旋体的形式存在非常有趣；由于酶是手性分子，产生天然产物的酶促反应应该是立体特异性的，并导致单一对映体产物。尽管文献中有几篇报道描述了从天然来源分离出的立体异构体的外消旋混合物，但尚未对这些有趣的外消旋天然产物进行全面综述。近年来发现了更多的天然外消旋体及其潜在的酶源，这使我们能够描述这类天然产物的分布和化学多样性，以丰富关于生物合成的讨论。在本综述中，我们描述了对映体对在自然界中的化学类别、出现情况和分布，并提供了有关用于其表征的分析方法的最新进展的见解。特别强调生物合成，包括天然外消旋体可能的酶促和非酶促形成及其药理学意义。
