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Contrasting effects of isocitrate dehydrogenase deletion on fluxes through enzymes of central metabolism in Escherichia coli.
FEMS Microbiol Lett. 2019 08 01; 366(15)FM

Abstract

Flux analysis is central to understanding cellular metabolism and successful manipulation of metabolic fluxes in microbial cell-factories. Isocitrate dehydrogenase (ICDH) deletion conferred contrasting effects on fluxes through substrate-level phosphorylation (SLP) reactions. While significantly increasing flux through pyruvate kinase, it diminishes flux through succinyl CoA synthetase and upregulates phosphotransacetylase (PTA) and acetate kinase (AK). In addition to acetate, the ICDH-less strain excretes pyruvate, citrate and isocitrate. While efflux to acetate excretion by the Escherichia coli parental strain and its ICDH-less derivative is a reflection of high throughput of glycolytic intermediates, excretion of pyruvate is a reflection of high throughput via pyruvate kinase. On the other hand, citrate and isocitrate excretion is a reflection of truncating the Krebs cycle at the level of ICDH. Furthermore, another striking finding is the inability of the ICDH-less cultures to utilize acetate as a source of carbon despite the availability of an adequate supply of extracellular glutamate (for biosynthesis) and elevated levels of AK and PTA (for acetate uptake). This striking observation is now explicable in the light of the newly proposed hypothesis that the expression of the ace operon enzymes is controlled in response to a minimum threshold signal (ATP), which could not be achieved in the ICDH-less strain.

Authors+Show Affiliations

Elizade University, Ilara Mokin, Ondo State, Nigeria. University of Africa (UAT), Bayelsa State, Nigeria.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31504493

Citation

El-Mansi, Mansi. "Contrasting Effects of Isocitrate Dehydrogenase Deletion On Fluxes Through Enzymes of Central Metabolism in Escherichia Coli." FEMS Microbiology Letters, vol. 366, no. 15, 2019.
El-Mansi M. Contrasting effects of isocitrate dehydrogenase deletion on fluxes through enzymes of central metabolism in Escherichia coli. FEMS Microbiol Lett. 2019;366(15).
El-Mansi, M. (2019). Contrasting effects of isocitrate dehydrogenase deletion on fluxes through enzymes of central metabolism in Escherichia coli. FEMS Microbiology Letters, 366(15). https://doi.org/10.1093/femsle/fnz187
El-Mansi M. Contrasting Effects of Isocitrate Dehydrogenase Deletion On Fluxes Through Enzymes of Central Metabolism in Escherichia Coli. FEMS Microbiol Lett. 2019 08 1;366(15) PubMed PMID: 31504493.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contrasting effects of isocitrate dehydrogenase deletion on fluxes through enzymes of central metabolism in Escherichia coli. A1 - El-Mansi,Mansi, PY - 2019/04/29/received PY - 2019/08/29/accepted PY - 2019/9/11/pubmed PY - 2020/7/24/medline PY - 2019/9/11/entrez KW - Escherichia coli KW - acetate excretion KW - central metabolism KW - flux analysis KW - isocitrate dehydrogenase KW - pyruvate kinase JF - FEMS microbiology letters JO - FEMS Microbiol Lett VL - 366 IS - 15 N2 - Flux analysis is central to understanding cellular metabolism and successful manipulation of metabolic fluxes in microbial cell-factories. Isocitrate dehydrogenase (ICDH) deletion conferred contrasting effects on fluxes through substrate-level phosphorylation (SLP) reactions. While significantly increasing flux through pyruvate kinase, it diminishes flux through succinyl CoA synthetase and upregulates phosphotransacetylase (PTA) and acetate kinase (AK). In addition to acetate, the ICDH-less strain excretes pyruvate, citrate and isocitrate. While efflux to acetate excretion by the Escherichia coli parental strain and its ICDH-less derivative is a reflection of high throughput of glycolytic intermediates, excretion of pyruvate is a reflection of high throughput via pyruvate kinase. On the other hand, citrate and isocitrate excretion is a reflection of truncating the Krebs cycle at the level of ICDH. Furthermore, another striking finding is the inability of the ICDH-less cultures to utilize acetate as a source of carbon despite the availability of an adequate supply of extracellular glutamate (for biosynthesis) and elevated levels of AK and PTA (for acetate uptake). This striking observation is now explicable in the light of the newly proposed hypothesis that the expression of the ace operon enzymes is controlled in response to a minimum threshold signal (ATP), which could not be achieved in the ICDH-less strain. SN - 1574-6968 UR - https://www.unboundmedicine.com/medline/citation/31504493/Contrasting_effects_of_isocitrate_dehydrogenase_deletion_on_fluxes_through_enzymes_of_central_metabolism_in_Escherichia_coli_ DB - PRIME DP - Unbound Medicine ER -