Optimizing microbial networks through metabolic bypasses.

Autor: Orsi E; Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. Electronic address: enricoo@biosustain.dtu.dk., Claassens NJ; Laboratory of Microbiology, Wageningen University, Stippeneng 4, 6708 WE Wageningen, the Netherlands., Nikel PI; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Lindner SN; Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany; Department of Biochemistry, Charité Universitätsmedizin, Virchowweg 6, 10117 Berlin, Germany. Electronic address: steffen.lindner@charite.de.
Jazyk: angličtina
Zdroj: Biotechnology advances [Biotechnol Adv] 2022 Nov; Vol. 60, pp. 108035. Date of Electronic Publication: 2022 Sep 09.
DOI: 10.1016/j.biotechadv.2022.108035
Abstrakt: Metabolism has long been considered as a relatively stiff set of biochemical reactions. This somewhat outdated and dogmatic view has been challenged over the last years, as multiple studies exposed unprecedented plasticity of metabolism by exploring rational and evolutionary modifications within the metabolic network of cell factories. Of particular importance is the emergence of metabolic bypasses, which consist of enzymatic reaction(s) that support unnatural connections between metabolic nodes. Such novel topologies can be generated through the introduction of heterologous enzymes or by upregulating native enzymes (sometimes relying on promiscuous activities thereof). Altogether, the adoption of bypasses resulted in an expansion in the capacity of the host's metabolic network, which can be harnessed for bioproduction. In this review, we discuss modifications to the canonical architecture of central carbon metabolism derived from such bypasses towards six optimization purposes: stoichiometric gain, overcoming kinetic limitations, solving thermodynamic barriers, circumventing toxic intermediates, uncoupling product synthesis from biomass formation, and altering redox cofactor specificity. The metabolic costs associated with bypass-implementation are likewise discussed, including tailoring their design towards improving bioproduction.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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