Qi Xiaoquan, Bakht Saleha, Qin Bo, Leggett Mike, Hemmings Andrew, Mellon Fred, Eagles John, Werck-Reichhart Daniele, Schaller Hubert, Lesot Agnes, Melton Rachel, Osbourn Anne
Department of Metabolic Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom.
Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18848-53. doi: 10.1073/pnas.0607849103. Epub 2006 Nov 21.
CYP51 sterol demethylases are the only cytochrome P450 enzymes with a conserved function across the animal, fungal, and plant kingdoms (in the synthesis of essential sterols). These highly conserved enzymes, which are important targets for cholesterol-lowering drugs, antifungal agents, and herbicides, are regarded as the most ancient member cytochrome P450 family. Here we present a report of a CYP51 enzyme that has acquired a different function. We show that the plant enzyme AsCYP51H10 is dispensable for synthesis of essential sterols and has been recruited for the production of antimicrobial compounds (avenacins) that confer disease resistance in oats. The AsCyp51H10 gene is synonymous with Sad2, a gene that we previously had defined by mutation as being required for avenacin synthesis. In earlier work, we showed that Sad1, the gene encoding the first committed enzyme in the avenacin pathway (beta-amyrin synthase), had arisen by duplication and divergence of a cycloartenol synthase-like gene. Together these data indicate an intimate evolutionary connection between the sterol and avenacin pathways. Sad1 and Sad2 lie within 70 kb of each other and are expressed specifically in the epidermal cells of the root tip, the site of accumulation of avenacins. These findings raise intriguing questions about the recruitment, coevolution, and regulation of the components of this specialized defense-related metabolic pathway.
CYP51甾醇脱甲基酶是动物、真菌和植物界（在必需甾醇的合成中）唯一具有保守功能的细胞色素P450酶。这些高度保守的酶是降胆固醇药物、抗真菌剂和除草剂的重要靶点，被认为是细胞色素P450家族中最古老的成员。在此，我们报告了一种具有不同功能的CYP51酶。我们发现植物酶AsCYP51H10对于必需甾醇的合成并非必需，而是被用于产生赋予燕麦抗病性的抗菌化合物（燕麦 avenacins）。AsCyp51H10基因与Sad2同义，我们之前通过突变将Sad2定义为燕麦 avenacin合成所需的基因。在早期工作中，我们表明，编码燕麦 avenacin途径中第一个关键酶（β-香树脂醇合酶）的基因Sad1是由一个环阿屯醇合酶样基因通过复制和分化产生的。这些数据共同表明甾醇和燕麦 avenacin途径之间存在紧密的进化联系。Sad1和Sad2彼此相距70 kb以内，并且在根尖的表皮细胞中特异性表达，根尖是燕麦 avenacins积累的部位。这些发现引发了关于这一特殊的防御相关代谢途径的组成成分的招募、共同进化和调控的有趣问题。
