Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis
Parallel evolution of non-homologous isofunctional enzymes in methionine biosynthesis
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DOI：
10.1038/nchembio.2397
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发表时间：
2017-08-01
影响因子：
14.8
通讯作者：
de Berardinis, Veronique
中科院分区：
文献类型：
--
作者：
Bastard, Karine;Perret, Alain;de Berardinis, Veronique
酶功能的实验验证对于基因组解释至关重要，但它仍然具有挑战性，因为它不能扩大规模以适应基因组序列的不断积累。我们针对Meta和MetX酶家族解决了这个问题，所述酶家族是参与L-甲硫氨酸生物合成的酰基-L-高丝氨酸转移酶的遗传学上不相关的家族。这些家族的成员倾向于不正确的注释，因为假定MetX和Meta酶总是分别使用乙酰辅酶A和琥珀酰辅酶A。我们测定了来自不同物种的100种酶的酶活性，并通过基于蛋白质结构建模的活性位点的结构分类来解释结果。我们预测，目前存在于数据库中的来自这些家族的10，000个序列中的>60%被错误注释，并表明乙酰辅酶A最初是这些同功能酶的唯一底物，这些酶在最近的细菌中进化为专门使用琥珀酰辅酶A。我们还发现了真菌中MetX酶的一个不同亚组，其仅作为O-琥珀酰-L-丝氨酸转移酶参与L-半胱氨酸生物合成。
Experimental validation of enzyme function is crucial for genome interpretation, but it remains challenging because it cannot be scaled up to accommodate the constant accumulation of genome sequences. We tackled this issue for the MetA and MetX enzyme families, phylogenetically unrelated families of acyl-L-homoserine transferases involved in L-methionine biosynthesis. Members of these families are prone to incorrect annotation because MetX and MetA enzymes are assumed to always use acetyl-CoA and succinyl-CoA, respectively. We determined the enzymatic activities of 100 enzymes from diverse species, and interpreted the results by structural classification of active sites based on protein structure modeling. We predict that >60% of the 10,000 sequences from these families currently present in databases are incorrectly annotated, and suggest that acetylCoA was originally the sole substrate of these isofunctional enzymes, which evolved to use exclusively succinyl-CoA in the most recent bacteria. We also uncovered a divergent subgroup of MetX enzymes in fungi that participate only in L-cysteine biosynthesis as O-succinyl-L-serine transferases.