Increased glutarate production by blocking the glutaryl-CoA dehydrogenation pathway and a catabolic pathway involving L-2-hydroxyglutarate.
Increased glutarate production by blocking the glutaryl-CoA dehydrogenation pathway and a catabolic pathway involving L-2-hydroxyglutarate.
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通过阻断戊二酰辅酶A脱氢途径和涉及L-2-羟基戊二酸的分解代谢途径来增加戊二酸产量
DOI：
10.1038/s41467-018-04513-0
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发表时间：
2018-05-29
影响因子：
16.6
通讯作者：
Xu P
中科院分区：
文献类型：
--
作者：
Zhang M;Gao C;Guo X;Guo S;Kang Z;Xiao D;Yan J;Tao F;Zhang W;Dong W;Liu P;Yang C;Ma C;Xu P
戊二酸是在L-赖氨酸催化过程中产生的五碳平台化学物质。已知其可通过戊二酰-CoA脱氢途径分解代谢。在这里，我们发现恶臭假单胞菌KT 2440具有涉及1 -2-羟基戊二酸（1 -2-HG）的额外的戊二酸分解代谢途径，1 - 2-HG是由2-酮戊二酸（2-KG）产生的异常代谢物。在该途径中，CsiD（一种Fe 2 +/2-KG依赖性戊二酸羟化酶）能够将戊二酸转化为1 -2-HG，LhgO（一种1 -2-HG氧化酶）能够催化1 -2-HG转化为2-KG。我们构建了一个重组菌株，缺乏这两个戊二酸分解代谢途径。该菌可从L-赖氨酸转化为戊二酸，产率为0.85mol戊二酸/mol L-赖氨酸。因此，1 -2-HG脱氢酶和催化酶是恶臭假单胞菌KT 2440中戊二酰-CoA脱氢途径的代谢替代物; l-赖氨酸可以是生酮和生糖的。众所周知，五碳平台化学物质戊二酸可以通过戊二酰-CoA脱氢途径分解代谢。在这里，作者发现了一个额外的戊二酸分解代谢途径，涉及1 -2-羟基戊二酸，并显示通过阻断两个分解代谢途径增加戊二酸的产量。
Glutarate is a five carbon platform chemical produced during the catabolism of l-lysine. It is known that it can be catabolized through the glutaryl-CoA dehydrogenation pathway. Here, we discover that Pseudomonas putida KT2440 has an additional glutarate catabolic pathway involving l-2-hydroxyglutarate (l-2-HG), an abnormal metabolite produced from 2-ketoglutarate (2-KG). In this pathway, CsiD, a Fe2+/2-KG-dependent glutarate hydroxylase, is capable of converting glutarate into l-2-HG, and LhgO, an l-2-HG oxidase, can catalyze l-2-HG into 2-KG. We construct a recombinant strain that lacks both glutarate catabolic pathways. It can produce glutarate from l-lysine with a yield of 0.85 mol glutarate/mol l-lysine. Thus, l-2-HG anabolism and catabolism is a metabolic alternative to the glutaryl-CoA dehydrogenation pathway in P. putida KT2440; l-lysine can be both ketogenic and glucogenic. It is known that the five carbon platform chemical glutarate can be catabolized by the glutaryl-CoA dehydrogenation pathway. Here, the authors discover an additional glutarate catabolic pathway involving l-2-hydroxyglutarate and show increased glutarate production by blocking both catabolic pathways.
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DOI：
10.1073/pnas.1614102114
发表时间：
2017-02-07
影响因子：
11.1
作者：
Li, Hongde;Chawla, Geetanjali;Tennessen, Jason M.
通讯作者：
Tennessen, Jason M.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8
作者：
Chance, MR;Bresnick, AR;Wang, LK
通讯作者：
Wang, LK
影响因子：
12.7
作者：
Balss, Joerg;Pusch, Stefan;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
5.4
作者：
Knauer, Stefan H.;Hartl-Spiegelhauer, Olivia;Dobbek, Holger
通讯作者：
Dobbek, Holger