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Applications of transcriptional prof...

Kizer, Jeffery Lance.

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Applications of transcriptional profiling in the engineering of Escherichia coli for the production of anti-malarial therapeutics.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Applications of transcriptional profiling in the engineering of Escherichia coli for the production of anti-malarial therapeutics./
Author:	Kizer, Jeffery Lance.
Description:	180 p.
Notes:	Adviser: Jay D. Keasling.
Contained By:	Dissertation Abstracts International68-08B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3275473
ISBN:	9780549167914

Applications of transcriptional profiling in the engineering of Escherichia coli for the production of anti-malarial therapeutics.
Kizer, Jeffery Lance.

Applications of transcriptional profiling in the engineering of Escherichia coli for the production of anti-malarial therapeutics. - 180 p.

Adviser: Jay D. Keasling.

Thesis (Ph.D.)--University of California, Berkeley, 2007.

This body of work suggests that DNA microarrays, when combined with other complementary analysis methods, can be a powerful tool for the design of novel biochemical pathways in microbial hosts.

ISBN: 9780549167914Subjects--Topical Terms:

1017734
Biology, Microbiology.

Applications of transcriptional profiling in the engineering of Escherichia coli for the production of anti-malarial therapeutics.
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020 $a 9780549167914
035 $a (UMI)AAI3275473
035 $a AAI3275473
040 $a UMI $c UMI
100 1 $a Kizer, Jeffery Lance. $3 1285801
245 1 0 $a Applications of transcriptional profiling in the engineering of Escherichia coli for the production of anti-malarial therapeutics.
300 $a 180 p.
500 $a Adviser: Jay D. Keasling.
500 $a Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5405.
502 $a Thesis (Ph.D.)--University of California, Berkeley, 2007.
520 $a This body of work suggests that DNA microarrays, when combined with other complementary analysis methods, can be a powerful tool for the design of novel biochemical pathways in microbial hosts.
520 $a Engineering synthetic metabolic pathways in microbes for the production of pharmaceuticals and complex chemicals is an attractive alternative to chemical synthesis. However, in transferring large biosynthetic pathways to alternate hosts and manipulating expression levels, the native regulation of carbon flux through the pathway may be lost, leading to an accumulation of toxic intermediates and consumption of cellular cofactors, energy or vital biosynthetic precursors by the heterologous pathway. With the maturation of functional genomics analysis it is now feasible to identify modes of toxicity associated with the accumulation of foreign molecules in the engineered bacterium and elucidate the exact nature of metabolic burden associated with the expression of a novel biochemical pathway.
520 $a Previously, Escherichia coli was engineered to produce large quantities of the sesquiterpene precursor to artemisinic acid, amorpha-4-11-diene by creating a mevalonate-based isopentenyl pyrophosphate biosynthetic pathway 1 (Martin et al. 2003. Nat. Biotechnol. 21:796). The engineered E. coli produced high levels of isoprenoids, but further optimization lead to an imbalance in carbon flux and the accumulation of the pathway intermediate 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), which proved to be cytotoxic to E. coli. Using both DNA microarray analysis and metabolite profiling we have studied E. coli strains inhibited by the intracellular accumulation of HMG-CoA. Our results indicate HMG-CoA inhibits fatty acid biosynthesis in the microbial host leading to a generalized membrane stress.
520 $a In a second series of experiments we combined transcriptomic analysis with proteomic and metabolite profiling to explore the metabolic burden on the E. coli host induced by producing amorpha-4-11-diene via the exogenous isoprenoid pathway. This work discovered the alterations in the intracellular prenyl phosphate pool was leading to under-modification of tRNA's and inducing a high serine flux. This serine flux was detrimental to overall productivity and media designed to address the serine requirement increased amorpha-4-11-diene production 2-fold.
590 $a School code: 0028.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Engineering, Chemical. $3 1018531
690 $a 0410
690 $a 0487
690 $a 0542
710 2 $a University of California, Berkeley. $3 687832
773 0 $t Dissertation Abstracts International $g 68-08B.
790 $a 0028
790 1 0 $a Keasling, Jay D., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3275473