Engineering dynamic pathway regulation using stress-response promoters
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Engineering dynamic pathway regulation using stress-response promoters. / Dahl, Robert H; Zhang, Fuzhong; Alonso-Gutierrez, Jorge; Baidoo, Edward; Batth, Tanveer S; Redding-Johanson, Alyssa M; Petzold, Christopher J; Mukhopadhyay, Aindrila; Lee, Taek Soon; Adams, Paul D; Keasling, Jay D.
In: Nature Biotechnology, 20.10.2013.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Engineering dynamic pathway regulation using stress-response promoters
AU - Dahl, Robert H
AU - Zhang, Fuzhong
AU - Alonso-Gutierrez, Jorge
AU - Baidoo, Edward
AU - Batth, Tanveer S
AU - Redding-Johanson, Alyssa M
AU - Petzold, Christopher J
AU - Mukhopadhyay, Aindrila
AU - Lee, Taek Soon
AU - Adams, Paul D
AU - Keasling, Jay D
PY - 2013/10/20
Y1 - 2013/10/20
N2 - Heterologous pathways used in metabolic engineering may produce intermediates toxic to the cell. Dynamic control of pathway enzymes could prevent the accumulation of these metabolites, but such a strategy requires sensors, which are largely unknown, that can detect and respond to the metabolite. Here we applied whole-genome transcript arrays to identify promoters that respond to the accumulation of toxic intermediates, and then used these promoters to control accumulation of the intermediate and improve the final titers of a desired product. We apply this approach to regulate farnesyl pyrophosphate (FPP) production in the isoprenoid biosynthetic pathway in Escherichia coli. This strategy improved production of amorphadiene, the final product, by twofold over that from inducible or constitutive promoters, eliminated the need for expensive inducers, reduced acetate accumulation and improved growth. We extended this approach to another toxic intermediate to demonstrate the broad utility of identifying novel sensor-regulator systems for dynamic regulation.
AB - Heterologous pathways used in metabolic engineering may produce intermediates toxic to the cell. Dynamic control of pathway enzymes could prevent the accumulation of these metabolites, but such a strategy requires sensors, which are largely unknown, that can detect and respond to the metabolite. Here we applied whole-genome transcript arrays to identify promoters that respond to the accumulation of toxic intermediates, and then used these promoters to control accumulation of the intermediate and improve the final titers of a desired product. We apply this approach to regulate farnesyl pyrophosphate (FPP) production in the isoprenoid biosynthetic pathway in Escherichia coli. This strategy improved production of amorphadiene, the final product, by twofold over that from inducible or constitutive promoters, eliminated the need for expensive inducers, reduced acetate accumulation and improved growth. We extended this approach to another toxic intermediate to demonstrate the broad utility of identifying novel sensor-regulator systems for dynamic regulation.
U2 - 10.1038/nbt.2689
DO - 10.1038/nbt.2689
M3 - Journal article
C2 - 24142050
JO - Nature Biotechnology
JF - Nature Biotechnology
SN - 1087-0156
ER -
ID: 68163506