Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and Derivatives

Microbially produced carboxylic acids (CAs) are considered key players in the implementation of more sustainable industrial processes due to their potential to replace a set of oil-derived commodity chemicals. Most CAs are intermediates of microbial central carbon metabolism, and therefore, a bioche...

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Main Authors: Ana Vila-Santa, Fernão C. Mendes, Frederico C. Ferreira, Kristala L. J. Prather, Nuno P. Mira
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/7/12/1020
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author Ana Vila-Santa
Fernão C. Mendes
Frederico C. Ferreira
Kristala L. J. Prather
Nuno P. Mira
author_facet Ana Vila-Santa
Fernão C. Mendes
Frederico C. Ferreira
Kristala L. J. Prather
Nuno P. Mira
author_sort Ana Vila-Santa
collection DOAJ
description Microbially produced carboxylic acids (CAs) are considered key players in the implementation of more sustainable industrial processes due to their potential to replace a set of oil-derived commodity chemicals. Most CAs are intermediates of microbial central carbon metabolism, and therefore, a biochemical production pathway is described and can be transferred to a host of choice to enable/improve production at an industrial scale. However, for some CAs, the implementation of this approach is difficult, either because they do not occur naturally (as is the case for levulinic acid) or because the described production pathway cannot be easily ported (as it is the case for adipic, muconic or glucaric acids). Synthetic biology has been reshaping the range of molecules that can be produced by microbial cells by setting new-to-nature pathways that leverage on enzyme arrangements not observed in vivo, often in association with the use of substrates that are not enzymes’ natural ones. In this review, we provide an overview of how the establishment of synthetic pathways, assisted by computational tools for metabolic retrobiosynthesis, has been applied to the field of CA production. The translation of these efforts in bridging the gap between the synthesis of CAs and of their more interesting derivatives, often themselves non-naturally occurring molecules, is also reviewed using as case studies the production of methacrylic, methylmethacrylic and poly-lactic acids.
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spelling doaj.art-4ce2d9be84f04029b7c31a9543dc466c2023-11-23T09:04:42ZengMDPI AGJournal of Fungi2309-608X2021-11-01712102010.3390/jof7121020Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and DerivativesAna Vila-Santa0Fernão C. Mendes1Frederico C. Ferreira2Kristala L. J. Prather3Nuno P. Mira4Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Department of Bioengineering, University of Lisbon, 1049-001 Lisbon, PortugalInstitute for Bioengineering and Biosciences, Instituto Superior Técnico, Department of Bioengineering, University of Lisbon, 1049-001 Lisbon, PortugalInstitute for Bioengineering and Biosciences, Instituto Superior Técnico, Department of Bioengineering, University of Lisbon, 1049-001 Lisbon, PortugalDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USAInstitute for Bioengineering and Biosciences, Instituto Superior Técnico, Department of Bioengineering, University of Lisbon, 1049-001 Lisbon, PortugalMicrobially produced carboxylic acids (CAs) are considered key players in the implementation of more sustainable industrial processes due to their potential to replace a set of oil-derived commodity chemicals. Most CAs are intermediates of microbial central carbon metabolism, and therefore, a biochemical production pathway is described and can be transferred to a host of choice to enable/improve production at an industrial scale. However, for some CAs, the implementation of this approach is difficult, either because they do not occur naturally (as is the case for levulinic acid) or because the described production pathway cannot be easily ported (as it is the case for adipic, muconic or glucaric acids). Synthetic biology has been reshaping the range of molecules that can be produced by microbial cells by setting new-to-nature pathways that leverage on enzyme arrangements not observed in vivo, often in association with the use of substrates that are not enzymes’ natural ones. In this review, we provide an overview of how the establishment of synthetic pathways, assisted by computational tools for metabolic retrobiosynthesis, has been applied to the field of CA production. The translation of these efforts in bridging the gap between the synthesis of CAs and of their more interesting derivatives, often themselves non-naturally occurring molecules, is also reviewed using as case studies the production of methacrylic, methylmethacrylic and poly-lactic acids.https://www.mdpi.com/2309-608X/7/12/1020carboxylic acidspathway prospectingmicrobial cell factoriessynthetic biologylevulinic acidadipic acid
spellingShingle Ana Vila-Santa
Fernão C. Mendes
Frederico C. Ferreira
Kristala L. J. Prather
Nuno P. Mira
Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and Derivatives
Journal of Fungi
carboxylic acids
pathway prospecting
microbial cell factories
synthetic biology
levulinic acid
adipic acid
title Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and Derivatives
title_full Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and Derivatives
title_fullStr Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and Derivatives
title_full_unstemmed Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and Derivatives
title_short Implementation of Synthetic Pathways to Foster Microbe-Based Production of Non-Naturally Occurring Carboxylic Acids and Derivatives
title_sort implementation of synthetic pathways to foster microbe based production of non naturally occurring carboxylic acids and derivatives
topic carboxylic acids
pathway prospecting
microbial cell factories
synthetic biology
levulinic acid
adipic acid
url https://www.mdpi.com/2309-608X/7/12/1020
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