Plant Biochemistry Laboratory, Department of Plant Biology and Biotechnology, University of Copenhagen, Frederiksberg, Denmark.
FEBS J. 2012 May;279(9):1545-62. doi: 10.1111/j.1742-4658.2011.08469.x. Epub 2012 Feb 1.
Nitrile formation in plants involves the activity of cytochrome P450s. Hydroxynitrile glucosides are widespread among plants but generally do not occur in glucosinolate producing species. Alliaria petiolata (garlic mustard, Brassicaceae) is the only species known to produce glucosinolates as well as a γ-hydroxynitrile glucoside. Furthermore, A. petiolata has been described to release diffusible cyanide, which indicates the presence of unidentified cyanogenic glucoside(s). Our research on A. petiolata addresses the molecular evolution of P450s. By integrating current knowledge about glucosinolate and hydroxynitrile glucoside biosynthesis in other species and new visions on recurrent evolution of hydroxynitrile glucoside biosynthesis, we propose a pathway for biosynthesis of the γ-hydroxynitrile glucoside, alliarinoside. Homomethionine and the corresponding oxime are suggested as shared intermediates in the biosynthesis of alliarinoside and 2-propenyl glucosinolate. The first committed step in the alliarinoside pathway is envisioned to be catalysed by a P450, which has been recruited to metabolize the oxime. Furthermore, alliarinoside biosynthesis is suggested to involve enzyme activities common to secondary modification of glucosinolates. Thus, we argue that biosynthesis of alliarinoside may be the first known case of a hydroxynitrile glucoside pathway having evolved from the glucosinolate pathway. An intriguing question is whether the proposed hydroxynitrile intermediate may also be converted to novel homomethionine-derived cyanogenic glucoside(s), which could release cyanide. Elucidation of the pathway for biosynthesis of alliarinoside and other putative hydroxynitrile glucosides in A. petiolata is envisioned to offer significant new knowledge on the emerging picture of P450 functional dynamics as a basis for recurrent evolution of pathways for bioactive natural product biosynthesis.
植物中的腈形成涉及细胞色素 P450s 的活性。羟腈葡萄糖苷广泛存在于植物中，但通常不存在于含硫葡萄糖苷的物种中。大蒜芥（Alliaria petiolata，十字花科）是唯一已知既能产生硫代葡萄糖苷又能产生γ-羟腈葡萄糖苷的物种。此外，大蒜芥已被描述为释放可扩散的氰化物，这表明存在未鉴定的氰苷。我们对大蒜芥的研究涉及 P450 的分子进化。通过整合其他物种中硫代葡萄糖苷和羟腈葡萄糖苷生物合成的现有知识以及对羟腈葡萄糖苷生物合成反复进化的新认识，我们提出了γ-羟腈葡萄糖苷，即大蒜芥苷的生物合成途径。同型蛋氨酸及其相应的肟被认为是大蒜芥苷和 2-丙烯基硫代葡萄糖苷生物合成的共同中间体。大蒜芥苷途径的第一步被设想由一种 P450 催化，该 P450 被招募来代谢肟。此外，大蒜芥苷生物合成被认为涉及到与硫代葡萄糖苷的次生修饰共同的酶活性。因此，我们认为大蒜芥苷的生物合成可能是第一个已知的羟腈葡萄糖苷途径从硫代葡萄糖苷途径进化而来的案例。一个有趣的问题是，所提出的羟腈中间产物是否也可以转化为新型的同型蛋氨酸衍生的氰苷，从而释放氰化物。阐明大蒜芥中大蒜芥苷和其他潜在羟腈葡萄糖苷的生物合成途径，有望为 P450 功能动力学的新兴图景提供重要的新知识，作为生物活性天然产物生物合成途径反复进化的基础。
