Integrated multi-omics unveil the impact of H-phosphinic analogs of glutamate and α-ketoglutarate on Escherichia coli metabolism

Giovannercole, Fabio; Gafeira Gonçalves, Luís; Armengaud, Jean; Varela Coelho, Ana; Khomutov, Alex; De Biase, Daniela

doi:10.1016/j.jbc.2024.107803

Journal of Biological Chemistry

2024

DOI: 10.1016/j.jbc.2024.107803

|View full text |Cite

Integrated multi-omics unveil the impact of H-phosphinic analogs of glutamate and α-ketoglutarate on Escherichia coli metabolism

Fabio Giovannercole,

Luís Gafeira Gonçalves,

Jean Armengaud

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Enzymatic Synthesis of Biologically Active H-Phosphinic Analogue of α-Ketoglutarate

Filonov,

Khomutov,

Tkachev

et al. 2024

Biomolecules

View full text Add to dashboard Cite

Amino acid analogues with a phosphorus-containing moiety replacing the carboxylic group are promising sources of biologically active compounds. The H-phosphinic group, with hydrogen–phosphorus–carbon (H-P-C) bonds and a flattened tetrahedral configuration, is a bioisostere of the carboxylic group. Consequently, amino-H-phosphinic acids undergo substrate-like enzymatic transformations, leading to new biologically active metabolites. Previous studies employing NMR-based metabolomic and proteomic analyses show that in Escherichia coli, α-KG-γ-PH (the distal H-phosphinic analogue of α-ketoglutarate) can be converted into L-Glu-γ-PH. Notably, α-KG-γ-PH and L-Glu-γ-PH are antibacterial compounds, but their intracellular targets only partially overlap. L-Glu-γ-PH is known to be a substrate of aspartate transaminase and glutamate decarboxylase, but its substrate properties with NAD+-dependent glutamate dehydrogenase (GDH) have never been investigated. Compounds containing P-H bonds are strong reducing agents; therefore, enzymatic NAD+-dependent oxidation is not self-evident. Herein, we demonstrate that L-Glu-γ-PH is a substrate of eukaryotic GDH and that the pH optimum of L-Glu-γ-PH NAD+-dependent oxidative deamination is shifted to a slightly alkaline pH range compared to L-glutamate. By 31P NMR, we observe that α-KG-γ-PH exists in a pH-dependent equilibrium of keto and germinal diol forms. Furthermore, the stereospecific enzymatic synthesis of α-KG-γ-PH from L-Glu-γ-PH using GDH is a possible route for its bio-based synthesis.

show abstract

Enzymatic Synthesis of Biologically Active H-Phosphinic Analogue of α-Ketoglutarate

Filonov,

Khomutov,

Tkachev

et al. 2024

Biomolecules

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Integrated multi-omics unveil the impact of H-phosphinic analogs of glutamate and α-ketoglutarate on Escherichia coli metabolism

Cited by 1 publication

References 83 publications

Enzymatic Synthesis of Biologically Active H-Phosphinic Analogue of α-Ketoglutarate

Enzymatic Synthesis of Biologically Active H-Phosphinic Analogue of α-Ketoglutarate

Contact Info

Product

Resources

About