Screening and modular design for metabolic pathway optimization

Biological conversion of substrate sugars to a variety of products is an increasingly popular option for chemical transformation due to its high specificity and because of significant interest in the use of renewable feedstocks. However, pathway optimization through metabolic engineering is often ne...

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Main Authors: Boock, Jason, Gupta, Apoorv, Jones, Kristala L.
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:en_US
Published: Elsevier 2017
Online Access:http://hdl.handle.net/1721.1/108027
https://orcid.org/0000-0002-5111-0969
https://orcid.org/0000-0002-6548-9420
https://orcid.org/0000-0003-0437-3157
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author Boock, Jason
Gupta, Apoorv
Jones, Kristala L.
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Boock, Jason
Gupta, Apoorv
Jones, Kristala L.
author_sort Boock, Jason
collection MIT
description Biological conversion of substrate sugars to a variety of products is an increasingly popular option for chemical transformation due to its high specificity and because of significant interest in the use of renewable feedstocks. However, pathway optimization through metabolic engineering is often needed to make such molecules economically at a relevant scale. Employing effective methods to search and narrow the immense pathway parameter space is essential to meet performance metrics such as high titer, yield and productivity with efficiency. This review focuses on two practices that increase the likelihood of finding a more advantageous pathway solution: implementing a screen to identify high producers and utilizing modular pathway design to streamline engineering efforts. While screens seek to couple product titer with a high-throughput measurement output, modular design aims to rationally construct pathways to allow parallel optimization of various units. Both of these methodologies have proven widely successful in metabolic engineering, with combinations of them resulting in synergistic enhancements to pathway optimization. This review will particularly highlight their utility for microbially derived acid and alcohol products, which are of interest as fuels and value added products.
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spelling mit-1721.1/1080272022-09-29T14:13:25Z Screening and modular design for metabolic pathway optimization Boock, Jason Gupta, Apoorv Jones, Kristala L. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Prather, Kristala L. Boock, Jason Gupta, Apoorv Jones, Kristala L. Biological conversion of substrate sugars to a variety of products is an increasingly popular option for chemical transformation due to its high specificity and because of significant interest in the use of renewable feedstocks. However, pathway optimization through metabolic engineering is often needed to make such molecules economically at a relevant scale. Employing effective methods to search and narrow the immense pathway parameter space is essential to meet performance metrics such as high titer, yield and productivity with efficiency. This review focuses on two practices that increase the likelihood of finding a more advantageous pathway solution: implementing a screen to identify high producers and utilizing modular pathway design to streamline engineering efforts. While screens seek to couple product titer with a high-throughput measurement output, modular design aims to rationally construct pathways to allow parallel optimization of various units. Both of these methodologies have proven widely successful in metabolic engineering, with combinations of them resulting in synergistic enhancements to pathway optimization. This review will particularly highlight their utility for microbially derived acid and alcohol products, which are of interest as fuels and value added products. National Science Foundation (U.S.) Synthetic Biology Engineering Research Center (EEC-0540879) United States. Department of Energy (DE-SC0012555) United States. Army Research Office (W911NF-09-0001) 2017-04-10T19:41:35Z 2017-04-10T19:41:35Z 2015-10 Article http://purl.org/eprint/type/JournalArticle 0958-1669 http://hdl.handle.net/1721.1/108027 Boock, Jason T, Gupta, Apoorv, and Prather, Kristala L J. “Screening and Modular Design for Metabolic Pathway Optimization.” Current Opinion in Biotechnology 36 (December 2015): 189–198. © 2015 Elsevier Ltd https://orcid.org/0000-0002-5111-0969 https://orcid.org/0000-0002-6548-9420 https://orcid.org/0000-0003-0437-3157 en_US http://dx.doi.org/10.1016/j.copbio.2015.08.013 Current Opinion in Biotechnology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Prof. Prather via Erja Kajosalo
spellingShingle Boock, Jason
Gupta, Apoorv
Jones, Kristala L.
Screening and modular design for metabolic pathway optimization
title Screening and modular design for metabolic pathway optimization
title_full Screening and modular design for metabolic pathway optimization
title_fullStr Screening and modular design for metabolic pathway optimization
title_full_unstemmed Screening and modular design for metabolic pathway optimization
title_short Screening and modular design for metabolic pathway optimization
title_sort screening and modular design for metabolic pathway optimization
url http://hdl.handle.net/1721.1/108027
https://orcid.org/0000-0002-5111-0969
https://orcid.org/0000-0002-6548-9420
https://orcid.org/0000-0003-0437-3157
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