A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories

Microbial cell factories (MCFs) are of considerable interest to convert low value renewable substrates to biofuels and high value chemicals. This review highlights the progress of computational models for the rational design of an MCF to produce a target bio-commodity. In particular, the rational de...

Full description

Bibliographic Details
Main Authors: Amanda K. Fisher, Benjamin G. Freedman, David R. Bevan, Ryan S. Senger
Format: Article
Language:English
Published: Elsevier 2014-08-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037014000257
_version_ 1811193435622735872
author Amanda K. Fisher
Benjamin G. Freedman
David R. Bevan
Ryan S. Senger
author_facet Amanda K. Fisher
Benjamin G. Freedman
David R. Bevan
Ryan S. Senger
author_sort Amanda K. Fisher
collection DOAJ
description Microbial cell factories (MCFs) are of considerable interest to convert low value renewable substrates to biofuels and high value chemicals. This review highlights the progress of computational models for the rational design of an MCF to produce a target bio-commodity. In particular, the rational design of an MCF involves: (i) product selection, (ii) de novo biosynthetic pathway identification (i.e., rational, heterologous, or artificial), (iii) MCF chassis selection, (iv) enzyme engineering of promiscuity to enable the formation of new products, and (v) metabolic engineering to ensure optimal use of the pathway by the MCF host. Computational tools such as (i) de novo biosynthetic pathway builders, (ii) docking, (iii) molecular dynamics (MD) and steered MD (SMD), and (iv) genome-scale metabolic flux modeling all play critical roles in the rational design of an MCF. Genome-scale metabolic flux models are of considerable use to the design process since they can reveal metabolic capabilities of MCF hosts. These can be used for host selection as well as optimizing precursors and cofactors of artificial de novo biosynthetic pathways. In addition, recent advances in genome-scale modeling have enabled the derivation of metabolic engineering strategies, which can be implemented using the genomic tools reviewed here as well.
first_indexed 2024-04-12T00:08:19Z
format Article
id doaj.art-84f99023410f44b38d2fdfe93ec44ee3
institution Directory Open Access Journal
issn 2001-0370
language English
last_indexed 2024-04-12T00:08:19Z
publishDate 2014-08-01
publisher Elsevier
record_format Article
series Computational and Structural Biotechnology Journal
spelling doaj.art-84f99023410f44b38d2fdfe93ec44ee32022-12-22T03:56:02ZengElsevierComputational and Structural Biotechnology Journal2001-03702014-08-011118919910.1016/j.csbj.2014.08.010A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factoriesAmanda K. Fisher0Benjamin G. Freedman1David R. Bevan2Ryan S. Senger3Department of Biological Systems Engineering, Virginia Tech, Blacksburg, VA, United StatesDepartment of Biological Systems Engineering, Virginia Tech, Blacksburg, VA, United StatesDepartment of Biochemistry, Virginia Tech, Blacksburg, VA, United StatesDepartment of Biological Systems Engineering, Virginia Tech, Blacksburg, VA, United StatesMicrobial cell factories (MCFs) are of considerable interest to convert low value renewable substrates to biofuels and high value chemicals. This review highlights the progress of computational models for the rational design of an MCF to produce a target bio-commodity. In particular, the rational design of an MCF involves: (i) product selection, (ii) de novo biosynthetic pathway identification (i.e., rational, heterologous, or artificial), (iii) MCF chassis selection, (iv) enzyme engineering of promiscuity to enable the formation of new products, and (v) metabolic engineering to ensure optimal use of the pathway by the MCF host. Computational tools such as (i) de novo biosynthetic pathway builders, (ii) docking, (iii) molecular dynamics (MD) and steered MD (SMD), and (iv) genome-scale metabolic flux modeling all play critical roles in the rational design of an MCF. Genome-scale metabolic flux models are of considerable use to the design process since they can reveal metabolic capabilities of MCF hosts. These can be used for host selection as well as optimizing precursors and cofactors of artificial de novo biosynthetic pathways. In addition, recent advances in genome-scale modeling have enabled the derivation of metabolic engineering strategies, which can be implemented using the genomic tools reviewed here as well.http://www.sciencedirect.com/science/article/pii/S2001037014000257Metabolic engineeringEnzyme engineeringMicrobial cell factoryGenome-scale modelDockingMolecular dynamics
spellingShingle Amanda K. Fisher
Benjamin G. Freedman
David R. Bevan
Ryan S. Senger
A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories
Computational and Structural Biotechnology Journal
Metabolic engineering
Enzyme engineering
Microbial cell factory
Genome-scale model
Docking
Molecular dynamics
title A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories
title_full A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories
title_fullStr A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories
title_full_unstemmed A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories
title_short A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories
title_sort review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories
topic Metabolic engineering
Enzyme engineering
Microbial cell factory
Genome-scale model
Docking
Molecular dynamics
url http://www.sciencedirect.com/science/article/pii/S2001037014000257
work_keys_str_mv AT amandakfisher areviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories
AT benjamingfreedman areviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories
AT davidrbevan areviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories
AT ryanssenger areviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories
AT amandakfisher reviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories
AT benjamingfreedman reviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories
AT davidrbevan reviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories
AT ryanssenger reviewofmetabolicandenzymaticengineeringstrategiesfordesigningandoptimizingperformanceofmicrobialcellfactories