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Exploitation of Hetero- and Phototrophic Metabolic Modules for Redox-Intensive Whole-Cell Biocatalysis
Open accessAbstract
The successful realization of a sustainable manufacturing bioprocess and the maximization of its production potential and capacity are the main concerns of a bioprocess engineer. A main step towards this endeavor is the development of an efficient biocatalyst. Isolated enzyme(s), microbial cells, or (immobilized) formulations thereof can serve as biocatalysts. Living cells feature, beside active enzymes, metabolic modules that can be exploited to support energy-dependent and multi-step enzyme-catalyzed reactions. Metabolism can sustainably supply necessary cofactors or cosubstrates at the expense of readily available and cheap resources, rendering external addition of costly cosubstrates unnecessary. However, for the development of an efficient whole-cell biocatalyst, in depth comprehension of metabolic modules and their interconnection with cell growth, maintenance, and product formation is indispensable. In order to maximize the flux through biosynthetic reactions and pathways to an industrially relevant product and respective key performance indices (i.e., titer, yield, and productivity), existing metabolic modules can be redesigned and/or novel artificial ones established. This review focuses on whole-cell bioconversions that are coupled to heterotrophic or phototrophic metabolism and discusses metabolic engineering efforts aiming at 1) increasing regeneration and supply of redox equivalents, such as NAD(P/H), 2) blocking competing fluxes, and 3) increasing the availability of metabolites serving as (co)substrates of desired biosynthetic routes.
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“Nonetheless, competition with native metabolic processes frequently restricts the efficiency of heterologous pathway activity.”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [143]
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“Since cyanobacterial ATP and NADPH production is tightly linked to PET, pathway efficiency can be heavily affected by factors such as light intensity, carbon availability, and cellular redox balance [143].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [143]
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Metadata
- Authors
- Theodosiou, E., Tüllinghoff, A., Toepel, J., & Bühler, B.
- Affiliations
- Centre for Research and Technology Hellas (GR)
- Helmholtz Centre for Environmental Research (DE)
- Corresponding author
- Bühler, Bruno
- Venue
- Frontiers in Bioengineering and Biotechnology
- Publisher
- Frontiers Media SA
- Published
- 2022-04-13
- Volume
- 10
- Pages
- 855715-855715
- ISSN
- 2296-4185 (ISSN-L)
- PMC
- PMC9043136
- OpenAlex
- W4224125904
- Semantic Scholar
- e00eaee1b714c8d312839e3acb7eed6543ad4153
- Cited by
- 17
- References
- 239
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 1
- FWCI
- 0.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Bioengineering and Biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Helmholtz-Zentrum für Umweltforschung
- European Regional Development Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Biochemical and biochemical processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
- Keywords
- whole-cell biocatalysis, metabolic modules, heterotrophic metabolism, redox metabolism, NAD(P)H regeneration, metabolic engineering, flux control, bioprocess intensification
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