Entner-Doudoroff pathway in Synechocystis PCC 6803: Proposed regulatory roles and enzyme multifunctionalities

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12520%2F22%3A43904544" target="_blank" >RIV/60076658:12520/22:43904544 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.3389/fmicb.2022.967545" target="_blank" >https://doi.org/10.3389/fmicb.2022.967545</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fmicb.2022.967545" target="_blank" >10.3389/fmicb.2022.967545</a>

Result language

angličtina

Original language name

Entner-Doudoroff pathway in Synechocystis PCC 6803: Proposed regulatory roles and enzyme multifunctionalities

Original language description

The Entner-Doudoroff pathway (ED-P) was established in 2016 as the fourth glycolytic pathway in Synechocystis sp. PCC 6803. ED-P consists of two reactions, the first catalyzed by 6-phosphogluconate dehydratase (EDD), the second by keto3-deoxygluconate-6-phosphate aldolase/4-hydroxy-2-oxoglutarate aldolase (EDA). ED-P was previously concluded to be a widespread (similar to 92%) pathway among cyanobacteria, but current bioinformatic analysis estimated the occurrence of ED-P to be either scarce (similar to 1%) or uncommon (similar to 47%), depending if dihydroxy-acid dehydratase (ilvD) also functions as EDD (currently assumed). Thus, the biochemical characterization of ilvD is a task pending to resolve this uncertainty. Next, we have provided new insights into several single and double glycolytic mutants based on kinetic model of central carbon metabolism of Synechocystis. The model predicted that silencing 6-phosphogluconate dehydrogenase (gnd) could be coupled with similar to 90% down-regulation of G6P-dehydrogenase, also limiting the metabolic flux via ED-P. Furthermore, our metabolic flux estimation implied that growth impairment linked to silenced EDA under mixotrophic conditions is not caused by diminished carbon flux via ED-P but rather by a missing mechanism related to the role of EDA in metabolism. We proposed two possible, mutually non-exclusive explanations: (i) Delta eda leads to disrupted carbon catabolite repression, regulated by 2-keto3-deoxygluconate-6-phosphate (ED-P intermediate), and (ii) EDA catalyzes the interconversion between glyoxylate and 4-hydroxy-2-oxoglutarate + pyruvate in the proximity of TCA cycle, possibly effecting the levels of 2-oxoglutarate under Delta eda. We have also proposed a new pathway from EDA toward proline, which could explain the proline accumulation under Delta eda. In addition, the presented in silico method provides an alternative to C-13 metabolic flux analysis for marginal metabolic pathways around/below the threshold of ultrasensitive LC-MS. Finally, our in silico analysis provided alternative explanations for the role of ED-P in Synechocystis while identifying some severe uncertainties.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Project

<a href="/en/project/LM2018099" target="_blank" >LM2018099: South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Microbiology

ISSN

1664-302X

e-ISSN

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Volume of the periodical

13

Issue of the periodical within the volume

neuvedeno

Country of publishing house

CH - SWITZERLAND

Number of pages

12

Pages from-to

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UT code for WoS article

000848018400001

EID of the result in the Scopus database

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