Reactive Enamines and Imines In Vivo: Lessons from the RidA Paradigm

Overview

Journal Trends Biochem Sci

Specialty Biochemistry

Date 2019 May 20

PMID 31103411

Citations 23

Authors

Andrew J Borchert

Dustin C Ernst

Diana M Downs

Affiliations

Soon will be listed here.

Abstract

Metabolic networks are webs of integrated reactions organized to maximize growth and replication while minimizing the detrimental impact that reactive metabolites can have on fitness. Enamines and imines, such as 2-aminoacrylate (2AA), are reactive metabolites produced as short-lived intermediates in a number of enzymatic processes. Left unchecked, the inherent reactivity of enamines and imines may perturb the metabolic network. Genetic and biochemical studies have outlined a role for the broadly conserved reactive intermediate deaminase (Rid) (YjgF/YER057c/UK114) protein family, in particular RidA, in catalyzing the hydrolysis of enamines and imines to their ketone product. Herein, we discuss new findings regarding the biological significance of enamine and imine production and outline the importance of RidA in controlling the accumulation of reactive metabolites.

Citing Articles

Interpreting the role of antioxidants in vivo: A cautionary tale.

Downs D, Poole R Mol Microbiol. 2024; 122(1):129-132.

PMID: 38960396 PMC: 11260230. DOI: 10.1111/mmi.15292.

Site-directed mutagenesis reveals the interplay between stability, structure, and enzymatic activity in RidA from Capra hircus.

Rizzi G, Digiovanni S, Degani G, Barbiroli A, Di Pisa F, Popolo L Protein Sci. 2024; 33(6):e5036.

PMID: 38801230 PMC: 11129622. DOI: 10.1002/pro.5036.

Tetrahydrofolate levels influence 2-aminoacrylate stress in .

Shen W, Downs D J Bacteriol. 2024; 206(4):e0004224.

PMID: 38563759 PMC: 11025330. DOI: 10.1128/jb.00042-24.

Machine learning analysis of RB-TnSeq fitness data predicts functional gene modules in KT2440.

Borchert A, Bleem A, Lim H, Rychel K, Dooley K, Kellermyer Z mSystems. 2024; 9(3):e0094223.

PMID: 38323821 PMC: 10949508. DOI: 10.1128/msystems.00942-23.

Modulators of a robust and efficient metabolism: Perspective and insights from the Rid superfamily of proteins.

Fulton R, Downs D Adv Microb Physiol. 2023; 83:117-179.

PMID: 37507158 PMC: 10642521. DOI: 10.1016/bs.ampbs.2023.04.001.

References

Merigliano C, Mascolo E, Burla R, Saggio I, Verni F . The Relationship Between Vitamin B6, Diabetes and Cancer. Front Genet. 2018; 9:388. PMC: 6146109. DOI: 10.3389/fgene.2018.00388. View

Menon S, Ragsdale S . Evidence that carbon monoxide is an obligatory intermediate in anaerobic acetyl-CoA synthesis. Biochemistry. 1996; 35(37):12119-25. DOI: 10.1021/bi961014d. View

Irons J, Hodge-Hanson K, Downs D . PA5339, a RidA Homolog, Is Required for Full Growth in Pseudomonas aeruginosa. J Bacteriol. 2018; 200(22). PMC: 6199476. DOI: 10.1128/JB.00434-18. View

Ernst D, Downs D . Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in . mBio. 2018; 9(1). PMC: 5829821. DOI: 10.1128/mBio.00084-18. View

Borchert A, Downs D . The Response to 2-Aminoacrylate Differs in Escherichia coli and Salmonella enterica, despite Shared Metabolic Components. J Bacteriol. 2017; 199(14). PMC: 5494748. DOI: 10.1128/JB.00140-17. View

Jhee K, Yang L, Ahmed S, McPhie P, Rowlett R, Miles E . Mutation of an active site residue of tryptophan synthase (beta-serine 377) alters cofactor chemistry. J Biol Chem. 1998; 273(19):11417-22. DOI: 10.1074/jbc.273.19.11417. View

Keller M, Piedrafita G, Ralser M . The widespread role of non-enzymatic reactions in cellular metabolism. Curr Opin Biotechnol. 2015; 34:153-61. PMC: 4728180. DOI: 10.1016/j.copbio.2014.12.020. View

Steffen-Munsberg F, Vickers C, Kohls H, Land H, Mallin H, Nobili A . Bioinformatic analysis of a PLP-dependent enzyme superfamily suitable for biocatalytic applications. Biotechnol Adv. 2015; 33(5):566-604. DOI: 10.1016/j.biotechadv.2014.12.012. View

Gorham S, Light N, Diamond A, Willins M, Bailey A, Wess T . Effect of chemical modifications on the susceptibility of collagen to proteolysis. II. Dehydrothermal crosslinking. Int J Biol Macromol. 1992; 14(3):129-38. DOI: 10.1016/s0141-8130(05)80002-9. View

10.

Lambrecht J, Downs D . Anthranilate phosphoribosyl transferase (TrpD) generates phosphoribosylamine for thiamine synthesis from enamines and phosphoribosyl pyrophosphate. ACS Chem Biol. 2012; 8(1):242-8. PMC: 3549051. DOI: 10.1021/cb300364k. View

11.

Niehaus T, Nguyen T, Gidda S, Elbadawi-Sidhu M, Lambrecht J, McCarty D . Arabidopsis and maize RidA proteins preempt reactive enamine/imine damage to branched-chain amino acid biosynthesis in plastids. Plant Cell. 2014; 26(7):3010-22. PMC: 4145128. DOI: 10.1105/tpc.114.126854. View

12.

Phillips A, Wood W . The mechanism of action of 5'-adenylic acid-activated threonine dehydrase. J Biol Chem. 1965; 240(12):4703-9. View

13.

Fisher H, Srinivasan R, Rougvie A . Glutamate dehydrogenase catalyzes the reduction of a Schiff base (delta 1-pyrroline-2-carboxylic acid) by NADPH. J Biol Chem. 1982; 257(22):13208-10. View

14.

Semchyshyn H . Reactive carbonyl species in vivo: generation and dual biological effects. ScientificWorldJournal. 2014; 2014:417842. PMC: 3918703. DOI: 10.1155/2014/417842. View

15.

Borchert A, Downs D . Analyses of variants of the Ser/Thr dehydratase IlvA provide insight into 2-aminoacrylate metabolism in . J Biol Chem. 2018; 293(50):19240-19249. PMC: 6302184. DOI: 10.1074/jbc.RA118.005626. View

16.

Watanabe A, Yoshimura T, Mikami B, Hayashi H, Kagamiyama H, Esaki N . Reaction mechanism of alanine racemase from Bacillus stearothermophilus: x-ray crystallographic studies of the enzyme bound with N-(5'-phosphopyridoxyl)alanine. J Biol Chem. 2002; 277(21):19166-72. DOI: 10.1074/jbc.M201615200. View

17.

Datta P, Bhadra R . Biodegradative threonine dehydratase. Reduction of ferricyanide by an intermediate of the enzyme-catalyzed reaction. Eur J Biochem. 1978; 91(2):527-32. DOI: 10.1111/j.1432-1033.1978.tb12706.x. View

18.

Burman J, Stevenson C, Sawers R, Lawson D . The crystal structure of Escherichia coli TdcF, a member of the highly conserved YjgF/YER057c/UK114 family. BMC Struct Biol. 2007; 7:30. PMC: 1884159. DOI: 10.1186/1472-6807-7-30. View

19.

Ernst D, Downs D . 2-Aminoacrylate Stress Induces a Context-Dependent Glycine Requirement in ridA Strains of Salmonella enterica. J Bacteriol. 2015; 198(3):536-43. PMC: 4719459. DOI: 10.1128/JB.00804-15. View

20.

Field D, Cotter P, Hill C, Ross R . Bioengineering Lantibiotics for Therapeutic Success. Front Microbiol. 2015; 6:1363. PMC: 4662063. DOI: 10.3389/fmicb.2015.01363. View