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Evolution of the chalcone-isomerase fold from fatty-acid binding to stereospecific catalysis

机译：查尔酮异构酶折叠从脂肪酸结合到立体定向催化的演变

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摘要

Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes. However, the lineage of the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI-catalysed conversion of chalcones to chiral (S)-fiavanones is a committed step in the production of plant flavonoids, compounds that contribute to attraction, defence and development. CHI operates near the diffusion limit with stereospecific control. Although associated primarily with plants, the CHI fold occurs in several other eukaryotic lineages and in some bacteria. Here we report crystal structures, ligand-binding properties and in vivo functional characterization of a non-catalytic CHI-fold family from plants. Arabidopsis thaliana contains five actively transcribed genes encoding CHI-fold proteins, three of which additionally encode amino-terminal chloroplast-transit sequences. These three CHI-fold proteins localize to plastids, the site of de novo fatty-acid biosynthesis in plant cells. Furthermore, their expression profiles correlate with those of core fatty-acid bio-synthetic enzymes, with maximal expression occurring in seeds and coinciding with increased fatty-acid storage in the developing embryo. In vitro, these proteins are fatty-acid-binding proteins (FAPs). FAP knockout A. thaliana plants show elevated a-linolenic acid levels and marked reproductive defects, including aberrant seed formation. Notably, the FAP discovery defines the adaptive evolution of a stereospecific and catalytically 'perfected' enzyme6 from a non-enzymatic ancestor over a defined period of plant evolution.
机译：专门的代谢酶生物合成具有重要生态意义的化学物质，通常与主要的代谢酶有共同的血统。但是，查尔酮异构酶（CHI）的谱系仍然未知。在维管植物中，CHI催化的查耳酮转化为手性（S）-黄烷酮是植物类黄酮（有助于吸引，防御和发育的化合物）生产中的重要步骤。 CHI通过立体定向控制在扩散极限附近操作。尽管CHI折叠主要与植物有关，但它在其他几个真核细胞谱系和某些细菌中也会发生。在这里，我们报告植物的非催化CHI折叠家族的晶体结构，配体结合特性和体内功能表征。拟南芥含有五个编码CHI折叠蛋白的活跃转录基因，其中三个还编码氨基末端的叶绿体转运序列。这三个CHI折叠蛋白位于质体中，质体是植物细胞中从头脂肪酸生物合成的位置。此外，它们的表达谱与核心脂肪酸生物合成酶的表达谱相关，最大表达出现在种子中，与脂肪酸在发育中的胚胎中的增加相吻合。在体外，这些蛋白质是脂肪酸结合蛋白（FAP）。 FAP敲除拟南芥植物显示升高的α-亚麻酸水平和明显的生殖缺陷，包括异常的种子形成。值得注意的是，FAP发现定义了在特定的植物进化时期内，非酶祖先的立体定向和催化“完美”酶6的适应性进化。

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  • 来源
    《Nature》 |2012年第7399期|p.530-533|共4页
  • 作者

    Micheline N. Ngaki; Gordon V. Louie; Ryan N. Philippe; Gerard Manning; Florence Pojer; Marianne E. Bowman; Ling Li; Elise Larsen; Eve Syrkin Wurtele; Joseph P. Noel;

  • 作者单位

    Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, Iowa 50011, USA;

    Howard Hughes Medical Institute, Jack H. Ski rball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Howard Hughes Medical Institute, Jack H. Ski rball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Razavi Newman Center for Bioinformatics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Howard Hughes Medical Institute, Jack H. Ski rball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Howard Hughes Medical Institute, Jack H. Ski rball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, Iowa 50011, USA;

    Howard Hughes Medical Institute, Jack H. Ski rball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, Iowa 50011, USA;

    Howard Hughes Medical Institute, Jack H. Ski rball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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