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Protein scaffolding is a natural phenomenon whereby proteins colocalize into macromolecular complexes via specific protein-protein interactions. In the case of metabolic enzymes, protein scaffolding drives metabolic flux through specific pathways by colocalizing enzyme active sites. Synthetic protein scaffolding is increasingly used as a mechanism to improve product specificity and yields in metabolic engineering projects. To date, synthetic scaffolding has focused primarily on soluble enzyme systems, but many metabolic pathways for high-value secondary metabolites depend on membrane-bound enzymes. The compositional diversity of biological membranes and general challenges associated with modifying membrane proteins complicate scaffolding with membrane-requiring enzymes. Several recent studies have introduced new approaches to protein scaffolding at membrane surfaces, with notable success in improving product yields from specific metabolic pathways. Copyright © 2019 Elsevier Ltd. All rights reserved.

Citation

James B Y H Behrendorff, Guillem Borràs-Gas, Mathias Pribil. Synthetic Protein Scaffolding at Biological Membranes. Trends in biotechnology. 2020 Apr;38(4):432-446

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PMID: 31718802

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