Improving fatty acids production by engineering dynamic pathway regulation and metabolic control
Name
Xu-2014-Improving fatty acid.pdf
Size
978 KB
Format
Adobe PDF
Checksum (MD5)
ae8701459a96c75e1a30997f90e57999
Author(s)
Xu, Peng
Li, Lingyun
Zhang, Fuming
Stephanopoulos, Gregory
Koffas, Mattheos
Date Issued
July 2014
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Xu, P., L. Li, F. Zhang, G. Stephanopoulos, and M. Koffas. “Improving Fatty Acids Production by Engineering Dynamic Pathway Regulation and Metabolic Control.” Proceedings of the National Academy of Sciences 111, no. 31 (July 21, 2014): 11299–11304. © 2014 National Academy of Sciences
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1406401111
