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Redesigning metabolism based on orthogonality principles
#MMPMID28555623
Pandit AV
; Srinivasan S
; Mahadevan R
Nat Commun
2017[May]; 8
(?): 15188
PMID28555623
show ga
Modifications made during metabolic engineering for overproduction of chemicals
have network-wide effects on cellular function due to ubiquitous metabolic
interactions. These interactions, that make metabolic network structures robust
and optimized for cell growth, act to constrain the capability of the cell
factory. To overcome these challenges, we explore the idea of an orthogonal
network structure that is designed to operate with minimal interaction between
chemical production pathways and the components of the network that produce
biomass. We show that this orthogonal pathway design approach has significant
advantages over contemporary growth-coupled approaches using a case study on
succinate production. We find that natural pathways, fundamentally linked to
biomass synthesis, are less orthogonal in comparison to synthetic pathways. We
suggest that the use of such orthogonal pathways can be highly amenable for
dynamic control of metabolism and have other implications for metabolic
engineering.
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