Increased glutarate production by blocking the glutaryl-CoA dehydrogenation pathway and a catabolic pathway involving L-2-hydroxyglutarate

Nature Communications
Manman ZhangPing Xu

Abstract

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.

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Citations

Jan 9, 2020·Environmental Microbiology·José M Luengo, Elías R Olivera
Dec 1, 2018·Nature Communications·Sebastian KnorrJörg S Hartig
Mar 7, 2020·Journal of Industrial Microbiology & Biotechnology·Xue SuiYu Deng
Aug 23, 2020·Applied and Environmental Microbiology·Mitchell G ThompsonJay D Keasling
Nov 24, 2020·Molecular Plant-microbe Interactions : MPMI·Nico NouwenEric Giraud
Nov 14, 2019·Metabolic Engineering Communications·Mitchell G ThompsonJay D Keasling
Sep 2, 2019·Trends in Biochemical Sciences·Guido T BommerMaria Veiga-da-Cunha
Feb 15, 2021·Biotechnology Advances·Wenna LiQipeng Yuan
Apr 29, 2021·Applied Microbiology and Biotechnology·Jiaping WangLiming Liu
Aug 8, 2021·Animals : an Open Access Journal From MDPI·Yu ZhangJiandui Mi
Sep 14, 2021·Frontiers in Bioengineering and Biotechnology·Yidong LiuCuiqing Ma
Jan 25, 2022·International Journal of Systematic and Evolutionary Microbiology·Franziskus HauthJörg S Hartig

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Datasets Mentioned

BETA
KT2440

Methods Mentioned

BETA
electrophoresis
reverse transcription-PCR
size exclusion chromatography
PCR
gel filtration

Software Mentioned

BLASTP
Interactive tree of life ( iTOL )
ClustalX
MEGA

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