Increasing the flux in metabolic pathways: A metabolic control analysis perspective

Abstract:

:The problems of engineering increased flux in metabolic pathways are analyzed in terms of the understanding provided by metabolic control analysis. Over-expression of a single enzyme is unlikely to be effective unless it is known to have a high flux control coefficient, which can be used as an approximate predictive tool. This is likely to rule out enzymes subject to feedback inhibition, because it transfers control downstream from the inhibited enzyme to the enzymes utilizing the feedback metabolite. Although abolishing feedback inhibition can restore flux control to an enzyme, it is also likely to cause large increases in the concentrations of metabolic intermediates. Simultaneous and coordinated over-expression of most of the enzymes in a pathway can, in principle, produce substantial flux increases without changes in metabolite levels, though technically it may be difficult to achieve. It is, however, closer to the method used by cells to change flux levels, where coordinated changes in the level of activity of pathway enzymes are the norm. Another option is to increase the demand for the pathway product, perhaps by increasing its rate of excretion or removal. Copyright 1998 John Wiley & Sons, Inc.

journal_name

Biotechnol Bioeng

authors

Fell DA

doi

10.1002/(sici)1097-0290(19980420)58:2/3<121::aid-b

subject

Has Abstract

pub_date

1998-04-05 00:00:00

pages

121-4

issue

2-3

eissn

0006-3592

issn

1097-0290

pii

10.1002/(SICI)1097-0290(19980420)58:2/3<121::AID-B

journal_volume

58

pub_type

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