Book Chapter10.1007/10_2013_221
Compartmentalization and metabolic channeling for multienzymatic biosynthesis: practical strategies and modeling approaches.
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TL;DR: This chapter provides an overview of numerous recent strategies for establishing compartmentalized multienzyme associations and constructed synthetic enzyme complexes and Perspectives on future studies of multienzymatic biosynthesis concerning compartmentalization and metabolic channeling.
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Abstract: The construction of efficient enzyme complexes for multienzymatic biosynthesis is of increasing interest in order to achieve maximum yield and to minimize the interference due to shortcomings that are typical for straightforward one-pot multienzyme catalysis. These include product or intermediate feedback inhibition, degeneration, and diffusive losses of reaction intermediates, consumption of co-factors, and others. The main mechanisms in nature to tackle these effects in transient or stable protein associations are the formation of metabolic channeling and microcompartments, processes that are desirable also for multienzymatic biosynthesis in vitro. This chapter provides an overview over two main aspects. First, numerous recent strategies for establishing compartmentalized multienzyme associations and constructed synthetic enzyme complexes are reviewed. Second, the computational methods at hand to investigate and optimize such associations systematically, especially with focus on large multienzyme complexes and metabolic channeling, are discussed. Perspectives on future studies of multienzymatic biosynthesis concerning compartmentalization and metabolic channeling are presented.
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Citations
Cell-free metabolic engineering: biomanufacturing beyond the cell.
TL;DR: In the coming years, CFME will offer exciting opportunities to debug and optimize biosynthetic pathways, carry out design‐build‐test iterations without re‐engineering organisms, and perform molecular transformations when bioconversion yields, productivities, or cellular toxicity limit commercial feasibility.
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Production of biofuels and biochemicals by in vitro synthetic biosystems: Opportunities and challenges.
TL;DR: The general design rules of in vitro synthetic pathways are presented with eight supporting examples: hydrogen, n-butanol, isobutanol, electricity, starch, lactate,1,3-propanediol, and poly-3-hydroxylbutyrate; a detailed economic analysis for enzymatic hydrogen production from carbohydrates is presented to illustrate some advantages of this system and the remaining challenges.
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Can enzyme proximity accelerate cascade reactions
A. R. Kuzmak,Sheiliza Carmali,Sheiliza Carmali,Eric von Lieres,Alan J. Russell,Svyatoslav Kondrat +5 more
TL;DR: It is demonstrated that proximity can have a more pronounced effect under crowding conditions in vivo, particularly that crowding can enhance the overall rates of channeled cascade reactions.
Metabolic engineering of synthetic cell-free systems: Strategies and applications
TL;DR: This review describes the major constrains of whole-cell-based biological processes and howcell-free systems have been used to overcome such limitations and provides new insights into cell-free and immobilization technologies for the improvement of synthetic metabolic systems.
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Annexation of a high-activity enzyme in a synthetic three-enzyme complex greatly decreases the degree of substrate channeling.
Chun You,Y.-H. Percival Zhang +1 more
TL;DR: The results suggested that the degree of substrate channeling in synthetic enzyme complexes depended on the enzyme choice, and the construction of synthetic enzyme enzymes in synthetic cascade pathways could be a very important tool to accrelerate rate-limiting steps controlled by low-activity enzymes.
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References
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TL;DR: A fusion gene which encoded a polypeptide comprised of 1116 amino acids was constructed using the α-amyl enzyme and glucoamylase cDNAs of Aspergillus shirousamii, and it was suggested that the characteristics are a result of the raw-starch-affinity site in the glu coamylases domain of the fusion protein.
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Anti-cancer drug development: computational strategies to identify and target proteins involved in cancer metabolism.
Lora Mak,Sonia Liggi,Lu Tan,Kanthida Kusonmano,Judith M. Rollinger,Alexios Koutsoukas,Robert C. Glen,Johannes Kirchmair +7 more
TL;DR: This review aims to provide a comprehensive overview of current strategies for computer-guided anti-cancer drug development, including machine learning techniques, the Connectivity Map and biological network analysis, and some of the many targets under investigation.
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Patterns of indirect protein interactions suggest a spatial organization to metabolism
TL;DR: Analysis of the metabolic and protein-protein interactions networks of Escherichia coli, yeast and humans is able to show that all three species have many more indirect protein interactions linking enzymes that share metabolites than would be expected by chance.
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