Abstract：
: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.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Dahl RH,Zhang F,Alonso-Gutierrez J,Baidoo E,Batth TS,Redding-Johanson AM,Petzold CJ,Mukhopadhyay A,Lee TS,Adams PD,Keasling JDdoi
10.1038/nbt.2689subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1039-46issue
11eissn
1087-0156issn
1546-1696pii
nbt.2689journal_volume
31pub_type
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