Spatial organization of enzymes for metabolic engineering.

Abstract:

:As synthetic pathways built from exogenous enzymes become more complicated, the probability of encountering undesired interactions with host organisms increases, thereby lowering product titer. An emerging strategy to combat this problem is to spatially organize pathway enzymes into multi-protein complexes, where high local concentrations of enzymes and metabolites may enhance flux and limit problematic interactions with the cellular milieu. Co-localizing enzymes using synthetic scaffolds has improved titers for multiple pathways. While lacking physical diffusion barriers, scaffolded systems could concentrate intermediates locally through a mechanism analogous to naturally occurring microdomains. A more direct strategy for compartmentalizing pathway components would be to encapsulate them within protein shells. Several classes of shells have been loaded with exogenous proteins and expressed successfully in industrial hosts. A critical challenge for achieving ideal pathway compartmentalization with protein shells will likely be evolving pores to selectively limit intermediate diffusion. Eventually, these tools should enhance our ability to rationally design metabolic pathways.

journal_name

Metab Eng

journal_title

Metabolic engineering

authors

Lee H,DeLoache WC,Dueber JE

doi

10.1016/j.ymben.2011.09.003

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

242-51

issue

3

eissn

1096-7176

issn

1096-7184

pii

S1096-7176(11)00093-0

journal_volume

14

pub_type

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