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Title: Metabolite damage and repair in metabolic engineering design

Abstract

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolicmore » engineering and synthetic biology projects.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Science Foundation (NSF)
OSTI Identifier:
1427485
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Metabolic Engineering
Additional Journal Information:
Journal Volume: 44; Journal Issue: C; Journal ID: ISSN 1096-7176
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
Enzyme promiscuity; Metabolic engineering; Metabolite damage; Metabolite repair; Side-reaction; Synthetic biology

Citation Formats

Sun, Jiayi, Jeffryes, James G., Henry, Christopher S., Bruner, Steven D., and Hanson, Andrew D.. Metabolite damage and repair in metabolic engineering design. United States: N. p., 2017. Web. doi:10.1016/j.ymben.2017.10.006.
Sun, Jiayi, Jeffryes, James G., Henry, Christopher S., Bruner, Steven D., & Hanson, Andrew D.. Metabolite damage and repair in metabolic engineering design. United States. doi:10.1016/j.ymben.2017.10.006.
Sun, Jiayi, Jeffryes, James G., Henry, Christopher S., Bruner, Steven D., and Hanson, Andrew D.. Wed . "Metabolite damage and repair in metabolic engineering design". United States. doi:10.1016/j.ymben.2017.10.006.
@article{osti_1427485,
title = {Metabolite damage and repair in metabolic engineering design},
author = {Sun, Jiayi and Jeffryes, James G. and Henry, Christopher S. and Bruner, Steven D. and Hanson, Andrew D.},
abstractNote = {The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.},
doi = {10.1016/j.ymben.2017.10.006},
journal = {Metabolic Engineering},
issn = {1096-7176},
number = C,
volume = 44,
place = {United States},
year = {2017},
month = {11}
}