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Growth-coupled Metabolic Engineering...

Mehrer, Christopher R.

Growth-coupled Metabolic Engineering for High-yield Chemical Production.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Growth-coupled Metabolic Engineering for High-yield Chemical Production.
Author:	Mehrer, Christopher R.
Published:	Ann Arbor : ProQuest Dissertations & Theses, 2019
Description:	184 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Notes:	Advisor: Pfleger, Brian F.
Contained By:	Dissertations Abstracts International81-04B.
Subject:	Chemical engineering.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13808170
ISBN:	9781687972880

Growth-coupled Metabolic Engineering for High-yield Chemical Production.
Mehrer, Christopher R.

Growth-coupled Metabolic Engineering for High-yield Chemical Production. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 184 p.

Source: Dissertations Abstracts International, Volume: 81-04, Section: B.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2019.

This item must not be sold to any third party vendors.

Oleochemicals are a class of organic chemicals found in fuels, materials, and consumer products. While oleochemicals are historically derived from petroleum and plant oils, microbial bioprocesses are seen as a major alternative to traditional chemical production. Improvements in bioprocess performance can be performed at multiple scales: molecular (gene expression), pathway, cell, small-scale fermentation, and fermentation scale-up. Here, two examples of oleochemical bioprocess development are examined. In the first example, a process to produce medium chain-length n-alcohols from glucose in Escherichia coli is developed. In this example, strain design was performed using a genome-scale metabolic model to build a growth-coupled strain to improve product yields. Techniques of synthetic biology were then employed to evaluate pathway variants and build an anaerobically autoinduced strain capable of producing 1.8 g/L of n-alcohols.In the second example, a bioconversion process to perform complete bioconversion of levulinic acid, a common catalytic product from biomass, to 2-butanone (methyl ethyl ketone) is developed. As with the first example, a genome-scale metabolic model was employed for growth-coupled strain design allowing for complete conversion. Following initial demonstration of the bioconversion, the process was integrated with furfuryl alcohol-derived levulinic acid, simulating a biomass-derived levulinic acid that would be employed in industrial production.Following the two, more full examples of bioprocess development, two other aspects of bioprocess development are studied. First, the beginnings of bioprocess scale-up are examined by scaling an octanoic acid-producing strain of E. coli to a high cell density fed-batch fermentation. A kinetic model is employed to analyze the fermentation and determine that octanoic acid toxicity is a major factor limiting process performance.Next, the focus is directed toward the beginning of bioprocess development from a strain-selection perspective. From previous knowledge concerning the phenotypic differences between E. coli strains MG1655 and LS5218, the genotypic differences between the two strains are examined. Finally, future directions of the field discussed. Particular focus is placed upon building useful kinetic models for strain design, scale-down and scale-up experiments, and potential new products for microbial process development.

ISBN: 9781687972880Subjects--Topical Terms:

206267
Chemical engineering.

Growth-coupled Metabolic Engineering for High-yield Chemical Production.
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300 $a 184 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
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506 $a This item must not be sold to any third party vendors.
520 $a Oleochemicals are a class of organic chemicals found in fuels, materials, and consumer products. While oleochemicals are historically derived from petroleum and plant oils, microbial bioprocesses are seen as a major alternative to traditional chemical production. Improvements in bioprocess performance can be performed at multiple scales: molecular (gene expression), pathway, cell, small-scale fermentation, and fermentation scale-up. Here, two examples of oleochemical bioprocess development are examined. In the first example, a process to produce medium chain-length n-alcohols from glucose in Escherichia coli is developed. In this example, strain design was performed using a genome-scale metabolic model to build a growth-coupled strain to improve product yields. Techniques of synthetic biology were then employed to evaluate pathway variants and build an anaerobically autoinduced strain capable of producing 1.8 g/L of n-alcohols.In the second example, a bioconversion process to perform complete bioconversion of levulinic acid, a common catalytic product from biomass, to 2-butanone (methyl ethyl ketone) is developed. As with the first example, a genome-scale metabolic model was employed for growth-coupled strain design allowing for complete conversion. Following initial demonstration of the bioconversion, the process was integrated with furfuryl alcohol-derived levulinic acid, simulating a biomass-derived levulinic acid that would be employed in industrial production.Following the two, more full examples of bioprocess development, two other aspects of bioprocess development are studied. First, the beginnings of bioprocess scale-up are examined by scaling an octanoic acid-producing strain of E. coli to a high cell density fed-batch fermentation. A kinetic model is employed to analyze the fermentation and determine that octanoic acid toxicity is a major factor limiting process performance.Next, the focus is directed toward the beginning of bioprocess development from a strain-selection perspective. From previous knowledge concerning the phenotypic differences between E. coli strains MG1655 and LS5218, the genotypic differences between the two strains are examined. Finally, future directions of the field discussed. Particular focus is placed upon building useful kinetic models for strain design, scale-down and scale-up experiments, and potential new products for microbial process development.
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