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Engineering Probiotic Lactic Acid Ba...

Bober, Josef R.

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Engineering Probiotic Lactic Acid Bacteria for Biomedical Applications.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Engineering Probiotic Lactic Acid Bacteria for Biomedical Applications./
Author:	Bober, Josef R.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	155 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
Contained By:	Dissertations Abstracts International80-12B.
Subject:	Bioengineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13878018
ISBN:	9781392242124

Engineering Probiotic Lactic Acid Bacteria for Biomedical Applications.
Bober, Josef R.

Engineering Probiotic Lactic Acid Bacteria for Biomedical Applications. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 155 p.

Source: Dissertations Abstracts International, Volume: 80-12, Section: B.

Thesis (Ph.D.)--Tufts University, 2019.

This item must not be added to any third party search indexes.

Correlations between the composition of the human microbiota and health status have sparked a rapidly growing interest in the intertwined complexities associated with these commensal microbial species. Large datasets of genetic, metabolic, proteomic etc. information can be generated through metagenomic and metatranscriptomics approaches rather easily; however, to elucidate the commensal mechanisms and benefits of these fastidious organisms, novel engineering techniques must accompany those observational measurements. Firmicutes, of which lactic acid bacteria (LAB) are members, make up the largest proportion of the human microbiota, yet few species are genetically tractable.Given their inherent safety and decades of food science research for fermentation processes, lactic-acid bacteria are ideal candidates for engineering novel biochemical production strains and the creation of living therapeutics for biomedical applications. In this work, we initially demonstrate the benefits of using Lactobacillus plantarum encapsulating the enzyme L-arabinose isomerase to overcome the thermodynamic, kinetic, and stability issues associated with galactose isomerization for tagatose production. We initially demonstrated the limitations to free-enzyme catalysis; challenging the traditional improvement approach of protein engineering, and systematically overcame each hurdle using a mesophilic enzyme encapsulated by a food-safe bacterium in a batch process resulting in the highest reported bioconversion.Next, we sought to engineer L. plantarum to rapidly sequester dietary lactose and galactose as a living therapeutic to remediate the toxicity of patients diagnosed with the rare genetic disorder galactosemia. Through this development, we studied the ability of L. plantarum to surface display heterologous proteins and enhanced the species ability to transport and metabolize carbohydrates.Overall, this thesis describes leveraging the beneficial probiotic properties of lactic acid bacteria for biomedical applications and emphasizes the need further improve upon currently available genetic tools to advance future applications.

ISBN: 9781392242124Subjects--Topical Terms:

657580
Bioengineering.
Subjects--Index Terms:

Lactic acid bacteria

Engineering Probiotic Lactic Acid Bacteria for Biomedical Applications.
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245 1 0 $a Engineering Probiotic Lactic Acid Bacteria for Biomedical Applications.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 155 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Nair, Nikhil U.
502 $a Thesis (Ph.D.)--Tufts University, 2019.
506 $a This item must not be added to any third party search indexes.
506 $a This item must not be sold to any third party vendors.
520 $a Correlations between the composition of the human microbiota and health status have sparked a rapidly growing interest in the intertwined complexities associated with these commensal microbial species. Large datasets of genetic, metabolic, proteomic etc. information can be generated through metagenomic and metatranscriptomics approaches rather easily; however, to elucidate the commensal mechanisms and benefits of these fastidious organisms, novel engineering techniques must accompany those observational measurements. Firmicutes, of which lactic acid bacteria (LAB) are members, make up the largest proportion of the human microbiota, yet few species are genetically tractable.Given their inherent safety and decades of food science research for fermentation processes, lactic-acid bacteria are ideal candidates for engineering novel biochemical production strains and the creation of living therapeutics for biomedical applications. In this work, we initially demonstrate the benefits of using Lactobacillus plantarum encapsulating the enzyme L-arabinose isomerase to overcome the thermodynamic, kinetic, and stability issues associated with galactose isomerization for tagatose production. We initially demonstrated the limitations to free-enzyme catalysis; challenging the traditional improvement approach of protein engineering, and systematically overcame each hurdle using a mesophilic enzyme encapsulated by a food-safe bacterium in a batch process resulting in the highest reported bioconversion.Next, we sought to engineer L. plantarum to rapidly sequester dietary lactose and galactose as a living therapeutic to remediate the toxicity of patients diagnosed with the rare genetic disorder galactosemia. Through this development, we studied the ability of L. plantarum to surface display heterologous proteins and enhanced the species ability to transport and metabolize carbohydrates.Overall, this thesis describes leveraging the beneficial probiotic properties of lactic acid bacteria for biomedical applications and emphasizes the need further improve upon currently available genetic tools to advance future applications.
590 $a School code: 0234.
650 4 $a Bioengineering. $3 657580
650 4 $a Chemical engineering. $3 560457
653 $a Lactic acid bacteria
653 $a Probiotics
690 $a 0202
690 $a 0542
710 2 $a Tufts University. $b Chemical and Biological Engineering. $3 1286908
773 0 $t Dissertations Abstracts International $g 80-12B.
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791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13878018