The tryptophan oxidation pathway in mosquitoes with emphasis on xanthurenic acid biosynthesis

Qian Han; Brenda T. Beerntsen; Jianyong Li

doi:10.1016/j.jinsphys.2006.09.004

Deglutarylation of GCDH by SIRT5 controls lysine metabolism in mice

10.1101/2020.06.28.176677 ◽

2020 ◽

Author(s):

Dhaval P. Bhatt ◽

C. Allie Mills ◽

Kristin A. Anderson ◽

Bárbara J. Henriques ◽

Tânia G. Lucas ◽

...

Keyword(s):

Feedback Loop ◽

Acid Metabolism ◽

Oxidation Pathway ◽

Wide Range ◽

Lysine Residues ◽

Tryptophan Oxidation ◽

The Impact ◽

The Relationship ◽

Lysine Catabolism ◽

Lysine Metabolism

ABSTRACTA wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be non-enzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme Sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH). We show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We then demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a model whereby a feedback loop exists within the lysine/tryptophan oxidation pathway, in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues, and can be relieved by SIRT5 deacylation activity.

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Optimization of (S)-3-Hydroxybutyric Acid Biosynthesis from Glucose through the Reversed Fatty Acid β-Oxidation Pathway by Recombinant Escherichia coli Strains

Applied Biochemistry and Microbiology ◽

10.1134/s0003683821020046 ◽

2021 ◽

Vol 57 (2) ◽

pp. 161-169

Author(s):

A. Yu. Gulevich ◽

A. Yu. Skorokhodova ◽

V. G. Debabov

Keyword(s):

Escherichia Coli ◽

Fatty Acid ◽

Product Yield ◽

Target Product ◽

Hydroxybutyric Acid ◽

Acid Biosynthesis ◽

Gene Encoding ◽

Oxidation Pathway ◽

Genes Encoding ◽

Primary Evaluation

Abstract The microaerobic synthesis of 3-hydroxybutyric acid by the Escherichia coli strain BOX3.1 ∆4 PL-atoB PL-tesB (MG1655 lacIQ, ∆ackA-pta, ∆poxB, ∆ldhA, ∆adhE, ∆fadE, PL-SDphi10-atoB, Ptrc-ideal-4-SDphi10-fadB, PL-SDphi10-tesB), which was previously directly engineered for the biosynthesis of the target compound from glucose through the reversed fatty acid β-oxidation pathway, was studied. A target product yield of 0.12 mol/mol was achieved. Inactivation of the nonspecific YciA thioesterase gene in the strain led to an increase in the yield of 3-hydroxybutyric acid to 0.15 mol/mol. For the optimization of biosynthesis of target product the strain MG∆4 PL-tesB (MG1655 ∆ackA-pta, ∆poxB, ∆ldhA, ∆adhE, PL-SDphi10-tesB) was engineered, and the genes encoding key enzymes of fatty acid β-oxidation were overexpressed in the strain from the plasmid pMW118m-atoB-fadB. The level of microaerobic synthesis of 3-hydroxybutyric acid by the strain MG∆4 PL-tesB (pMW118m-atoB-fadB) achieved in primary evaluation conditions reached 0.35 mol/mol. Inactivation in the strain of the gene of nonspecific thioesterase YciA led to only minor decrease in acetate byproduction. Further inactivation in the strain of gene encoding nonspecific thioesterase YdiI had virtually no effect on the level of synthesis of side products. Cultivation of the constructed strain MG∆4 PL-tesB ∆yciA (pMW118m-atoB-fadB) in bioreactor under the controlled conditions ensured achievement of a yield of 3‑hydroxybutyric acid amounting to 0.75 mol/mol.

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