In silico and in vivo analyses reveal key metabolic pathways enabling the fermentative utilization of glycerol in Escherichia coli

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dc.citation.firstpage289en_US
dc.citation.issueNumber1en_US
dc.citation.journalTitleMicrobial Biotechnologyen_US
dc.citation.lastpage304en_US
dc.citation.volumeNumber15en_US
dc.contributor.authorClomburg, James M.en_US
dc.contributor.authorCintolesi, Angelaen_US
dc.contributor.authorGonzalez, Ramonen_US
dc.date.accessioned2022-01-21T16:23:59Zen_US
dc.date.available2022-01-21T16:23:59Zen_US
dc.date.issued2022en_US
dc.description.abstractMost microorganisms can metabolize glycerol when external electron acceptors are available (i.e. under respiratory conditions). However, few can do so under fermentative conditions owing to the unique redox constraints imposed by the high degree of reduction of glycerol. Here, we utilize in silico analysis combined with in vivo genetic and biochemical approaches to investigate the fermentative metabolism of glycerol in Escherichia coli. We found that E. coli can achieve redox balance at alkaline pH by reducing protons to H2, complementing the previously reported role of 1,2-propanediol synthesis under acidic conditions. In this new redox balancing mode, H2 evolution is coupled to a respiratory glycerol dissimilation pathway composed of glycerol kinase (GK) and glycerol-3-phosphate (G3P) dehydrogenase (G3PDH). GK activates glycerol to G3P, which is further oxidized by G3PDH to generate reduced quinones that drive hydrogenase-dependent H2 evolution. Despite the importance of the GK-G3PDH route under alkaline conditions, we found that the NADH-generating glycerol dissimilation pathway via glycerol dehydrogenase (GldA) and phosphoenolpyruvate (PEP)-dependent dihydroxyacetone kinase (DHAK) was essential under both alkaline and acidic conditions. We assessed system-wide metabolic impacts of the constraints imposed by the PEP dependency of the GldA-DHAK route. This included the identification of enzymes and pathways that were not previously known to be involved in glycerol metabolisms such as PEP carboxykinase, PEP synthetase, multiple fructose-1,6-bisphosphatases and the fructose phosphate bypass.en_US
dc.identifier.citationClomburg, James M., Cintolesi, Angela and Gonzalez, Ramon. "In silico and in vivo analyses reveal key metabolic pathways enabling the fermentative utilization of glycerol in Escherichia coli." <i>Microbial Biotechnology,</i> 15, no. 1 (2022) Wiley: 289-304. https://doi.org/10.1111/1751-7915.13938.en_US
dc.identifier.digitalMicrobialBiotechnology-2021-Clomburgen_US
dc.identifier.doihttps://doi.org/10.1111/1751-7915.13938en_US
dc.identifier.urihttps://hdl.handle.net/1911/111932en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleIn silico and in vivo analyses reveal key metabolic pathways enabling the fermentative utilization of glycerol in Escherichia colien_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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