Molecular basis of the evolution of alternative tyrosine biosynthetic routes in plants
Molecular basis of the evolution of alternative tyrosine biosynthetic routes in plants
复制标题
DOI：
10.1038/nchembio.2414
复制
发表时间：
2017-09-01
影响因子：
14.8
通讯作者：
Maeda, Hiroshi A.
中科院分区：
文献类型：
--
作者：
Schenck, Craig A.;Holland, Cynthia K.;Maeda, Hiroshi A.
L酪氨酸(Tyr)是蛋白质合成所必需的，是许多对植物和人类健康至关重要的特殊代谢物的前体。酪氨酸可以通过两种不同的途径合成，即预苯酸脱氢酶(PDH，也称为TyrA(P))或芳香酸脱氢酶(ADH，也称为TyrA(A))，代表着初级代谢途径的独特分歧。目前尚不清楚这些可供选择的Tyr途径进化的分子基础。在这里，我们对最近分离的植物PDH和ADH酶进行了鉴定，获得了大豆PDH的X射线晶体结构，并鉴定了定义Tyra底物专一性和调控的单一氨基酸残基。突变的PDH与Tyr共结晶的结构表明，Asn222的取代赋予了ADH活性和Tyr敏感性。在不同的植物ADHS中相应残基的相互突变进一步引入了PDH活性和放松了Tyr的敏感性，突显了该残基在Tyra底物专一性中的关键作用，这是植物中替代Tyr生物合成途径进化的基础。
L-Tyrosine (Tyr) is essential for protein synthesis and is a precursor of numerous specialized metabolites crucial for plant and human health. Tyr can be synthesized via two alternative routes by different key regulatory TyrA family enzymes, prephenate dehydrogenase (PDH, also known as TyrA(p)) or arogenate dehydrogenase (ADH, also known as TyrA(a)), representing a unique divergence of primary metabolic pathways. The molecular foundation underlying the evolution of these alternative Tyr pathways is currently unknown. Here we characterized recently diverged plant PDH and ADH enzymes, obtained the X-ray crystal structure of soybean PDH, and identified a single amino acid residue that defines TyrA substrate specificity and regulation. Structures of mutated PDHs co-crystallized with Tyr indicate that substitutions of Asn222 confer ADH activity and Tyr sensitivity. Reciprocal mutagenesis of the corresponding residue in divergent plant ADHs further introduced PDH activity and relaxed Tyr sensitivity, highlighting the critical role of this residue in TyrA substrate specificity that underlies the evolution of alternative Tyr biosynthetic pathways in plants.