Improving fatty acids production by engineering dynamic pathway regulation and metabolic control.

Abstract:

:Global energy demand and environmental concerns have stimulated increasing efforts to produce carbon-neutral fuels directly from renewable resources. Microbially derived aliphatic hydrocarbons, the petroleum-replica fuels, have emerged as promising alternatives to meet this goal. However, engineering metabolic pathways with high productivity and yield requires dynamic redistribution of cellular resources and optimal control of pathway expression. Here we report a genetically encoded metabolic switch that enables dynamic regulation of fatty acids (FA) biosynthesis in Escherichia coli. The engineered strains were able to dynamically compensate the critical enzymes involved in the supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward FA biosynthesis. Implementation of this metabolic control resulted in an oscillatory malonyl-CoA pattern and a balanced metabolism between cell growth and product formation, yielding 15.7- and 2.1-fold improvement in FA titer compared with the wild-type strain and the strain carrying the uncontrolled metabolic pathway. This study provides a new paradigm in metabolic engineering to control and optimize metabolic pathways facilitating the high-yield production of other malonyl-CoA-derived compounds.

authors

Xu P,Li L,Zhang F,Stephanopoulos G,Koffas M

doi

10.1073/pnas.1406401111

subject

Has Abstract

pub_date

2014-08-05 00:00:00

pages

11299-304

issue

31

eissn

0027-8424

issn

1091-6490

pii

1406401111

journal_volume

111

pub_type

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