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Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate.

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Knorr S, Sinn M, Galetskiy D, Williams RM, Wang C, Müller N, Mayans O, Schleheck D, Hartig JS
OpenAccess logo Nat Commun 9 5071 (2018)
Related entries: 6gpe, 6hl8, 6hl9

Cited: 27 times
EuropePMC logo PMID: 30498244

Abstract

Lysine degradation has remained elusive in many organisms including Escherichia coli. Here we report catabolism of lysine to succinate in E. coli involving glutarate and L-2-hydroxyglutarate as intermediates. We show that CsiD acts as an α-ketoglutarate-dependent dioxygenase catalysing hydroxylation of glutarate to L-2-hydroxyglutarate. CsiD is found widespread in bacteria. We present crystal structures of CsiD in complex with glutarate, succinate, and the inhibitor N-oxalyl-glycine, demonstrating strong discrimination between the structurally related ligands. We show that L-2-hydroxyglutarate is converted to α-ketoglutarate by LhgO acting as a membrane-bound, ubiquinone-linked dehydrogenase. Lysine enters the pathway via 5-aminovalerate by the promiscuous enzymes GabT and GabD. We demonstrate that repression of the pathway by CsiR is relieved upon glutarate binding. In conclusion, lysine degradation provides an important link in central metabolism. Our results imply the gut microbiome as a potential source of glutarate and L-2-hydroxyglutarate associated with human diseases such as cancer and organic acidurias.

Reviews - 6gpn mentioned but not cited (1)

  1. Glutarate L-2-hydroxylase (CsiD/GlaH) is an archetype Fe(II)/2-oxoglutarate-dependent dioxygenase. Herr CQ, Macomber L, Kalliri E, Hausinger RP. Adv Protein Chem Struct Biol 117 63-90 (2019)


Reviews citing this publication (3)

  1. Evolutionary origin and functional diversification of aminotransferases. Koper K, Han SW, Pastor DC, Yoshikuni Y, Maeda HA. J Biol Chem 298 102122 (2022)
  2. Gut microbiota bridges dietary nutrients and host immunity. Fan L, Xia Y, Wang Y, Han D, Liu Y, Li J, Fu J, Wang L, Gan Z, Liu B, Fu J, Zhu C, Wu Z, Zhao J, Han H, Wu H, He Y, Tang Y, Zhang Q, Wang Y, Zhang F, Zong X, Yin J, Zhou X, Yang X, Wang J, Yin Y, Ren W. Sci China Life Sci 66 2466-2514 (2023)
  3. The role of the gut microbiome and microbial metabolism in mediating opioid-induced changes in the epigenome. Kolli U, Roy S. Front Microbiol 14 1233194 (2023)

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  1. Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes. Menni C, Zhu J, Le Roy CI, Mompeo O, Young K, Rebholz CM, Selvin E, North KE, Mohney RP, Bell JT, Boerwinkle E, Spector TD, Mangino M, Yu B, Valdes AM. Gut Microbes 11 1632-1642 (2020)
  2. Massively Parallel Fitness Profiling Reveals Multiple Novel Enzymes in Pseudomonas putida Lysine Metabolism. Thompson MG, Blake-Hedges JM, Cruz-Morales P, Barajas JF, Curran SC, Eiben CB, Harris NC, Benites VT, Gin JW, Sharpless WA, Twigg FF, Skyrud W, Krishna RN, Pereira JH, Baidoo EEK, Petzold CJ, Adams PD, Arkin AP, Deutschbauer AM, Keasling JD. mBio 10 e02577-18 (2019)
  3. Experimental and computational investigation of enzyme functional annotations uncovers misannotation in the EC 1.1.3.15 enzyme class. Rembeza E, Engqvist MKM. PLoS Comput Biol 17 e1009446 (2021)
  4. Fermentative Production of l-2-Hydroxyglutarate by Engineered Corynebacterium glutamicum via Pathway Extension of l-Lysine Biosynthesis. Prell C, Burgardt A, Meyer F, Wendisch VF. Front Bioeng Biotechnol 8 630476 (2020)
  5. Bacterial synthesis of C3-C5 diols via extending amino acid catabolism. Wang J, Li C, Zou Y, Yan Y. Proc Natl Acad Sci U S A 117 19159-19167 (2020)
  6. SAR11 Cells Rely on Enzyme Multifunctionality To Metabolize a Range of Polyamine Compounds. Noell SE, Barrell GE, Suffridge C, Morré J, Gable KP, Graff JR, VerWey BJ, Hellweger FL, Giovannoni SJ. mBio 12 e0109121 (2021)
  7. Uncovering a superfamily of nickel-dependent hydroxyacid racemases and epimerases. Desguin B, Urdiain-Arraiza J, Da Costa M, Fellner M, Hu J, Hausinger RP, Desmet T, Hols P, Soumillion P. Sci Rep 10 18123 (2020)
  8. Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in Pseudomonas putida KT2440. Zhang M, Kang Z, Guo X, Guo S, Xiao D, Liu Y, Ma C, Gao C, Xu P. mBio 10 e01570-19 (2019)
  9. An L-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR. Kang Z, Zhang M, Gao K, Zhang W, Meng W, Liu Y, Xiao D, Guo S, Ma C, Gao C, Xu P. Nat Commun 12 3619 (2021)
  10. Lead exposure and serum metabolite profiles in pregnant women in Mexico City. Niedzwiecki MM, Eggers S, Joshi A, Dolios G, Cantoral A, Lamadrid-Figueroa H, Amarasiriwardena C, Téllez-Rojo MM, Wright RO, Petrick L. Environ Health 20 125 (2021)
  11. Cadaverine Is a Switch in the Lysine Degradation Pathway in Pseudomonas aeruginosa Biofilm Identified by Untargeted Metabolomics. Leggett A, Li DW, Sindeldecker D, Staats A, Rigel N, Bruschweiler-Li L, Brüschweiler R, Stoodley P. Front Cell Infect Microbiol 12 833269 (2022)
  12. Immunometabolic and potential tumor-promoting changes in 3D cervical cell models infected with bacterial vaginosis-associated bacteria. Maarsingh JD, Łaniewski P, Herbst-Kralovetz MM. Commun Biol 5 725 (2022)
  13. Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration. Moon S, Tsay JJ, Lampert H, Md Dom ZI, Kostic AD, Smiles A, Niewczas MA. Sci Rep 11 8592 (2021)
  14. Genomic and Transcriptomic Investigation of the Physiological Response of the Methylotroph Bacillus methanolicus to 5-Aminovalerate. Haupka C, Brito LF, Busche T, Wibberg D, Wendisch VF. Front Microbiol 12 664598 (2021)
  15. An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism. Thompson MG, Blake-Hedges JM, Pereira JH, Hangasky JA, Belcher MS, Moore WM, Barajas JF, Cruz-Morales P, Washington LJ, Haushalter RW, Eiben CB, Liu Y, Skyrud W, Benites VT, Barnum TP, Baidoo EEK, Scheller HV, Marletta MA, Shih PM, Adams PD, Keasling JD. Nat Commun 11 2931 (2020)
  16. Cation Homeostasis: Coordinate Regulation of Polyamine and Magnesium Levels in Salmonella. Iwadate Y, Golubeva YA, Slauch JM. mBio 14 e0269822 (2023)
  17. Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii In Vivo. Li G, Shen W, Gong Y, Li M, Rao X, Liu Q, Yu Y, Zhou J, Zhu K, Yuan M, Shang W, Yang Y, Lu S, Wang J, Zhao Y. mSystems 7 e0033822 (2022)
  18. Insight into the Metabolic Profiles of Pb(II) Removing Microorganisms. Cilliers C, Chirwa EMN, Brink HG. Molecules 26 4008 (2021)
  19. Development of a 2-hydroxyglutarate production system by Corynebacterium glutamicum. Kataoka N, Matsushita K, Yakushi T. Appl Microbiol Biotechnol 107 5987-5997 (2023)
  20. Dynamic Changes in the Bacterial Community and Metabolic Profile during Fermentation of Low-Salt Shrimp Paste (Terasi). Helmi H, Astuti DI, Putri SP, Sato A, Laviña WA, Fukusaki E, Aditiawati P. Metabolites 12 118 (2022)
  21. Oxygenolytic sulfoquinovose degradation by an iron-dependent alkanesulfonate dioxygenase. Ye Z, Wei Y, Jiang L, Zhang Y. iScience 26 107803 (2023)
  22. Structure and biochemical characterization of l-2-hydroxyglutarate dehydrogenase and its role in the pathogenesis of l-2-hydroxyglutaric aciduria. Yang J, Chen X, Jin S, Ding J. J Biol Chem 300 105491 (2023)
  23. Zinc effects on bacteria: insights from Escherichia coli by multi-omics approach. Rihacek M, Kosaristanova L, Fialova T, Kuthanova M, Eichmeier A, Hakalova E, Cerny M, Berka M, Palkovicova J, Dolejska M, Svec P, Adam V, Zurek L, Cihalova K. mSystems 8 e0073323 (2023)


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