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Title: An end-to-end pipeline for succinic acid production at an industrially relevant scale using Issatchenkia orientalis

Journal Article · · Nature Communications

Abstract Microbial production of succinic acid (SA) at an industrially relevant scale has been hindered by high downstream processing costs arising from neutral pH fermentation for over three decades. Here, we metabolically engineer the acid-tolerant yeast Issatchenkia orientalis for SA production, attaining the highest titers in sugar-based media at low pH (pH 3) in fed-batch fermentations, i.e. 109.5 g/L in minimal medium and 104.6 g/L in sugarcane juice medium. We further perform batch fermentation using sugarcane juice medium in a pilot-scale fermenter (300×) and achieve 63.1 g/L of SA, which can be directly crystallized with a yield of 64.0%. Finally, we simulate an end-to-end low-pH SA production pipeline, and techno-economic analysis and life cycle assessment indicate our process is financially viable and can reduce greenhouse gas emissions by 34–90% relative to fossil-based production processes. We expect I. orientalis can serve as a general industrial platform for production of organic acids.

Sponsoring Organization:
USDOE
Grant/Contract Number:
SC0018420
OSTI ID:
2007441
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 14; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United Kingdom
Language:
English

References (64)

Succinic acid production derived from carbohydrates: An energy and greenhouse gas assessment of a platform chemical toward a bio-based economy journal August 2013
Process development and techno‐economic analysis of bio‐based succinic acid derived from pentoses integrated to a sugarcane biorefinery journal September 2017
Bio‐based succinic acid: an overview of strain development, substrate utilization, and downstream purification journal November 2019
Revitalizing the sugarcane industry by adding value to A‐molasses in biorefineries journal June 2020
Low‐pH production of d ‐lactic acid using newly isolated acid tolerant yeast Pichia kudriavzevii NG7 journal June 2018
Economic assessment of continuous processing for manufacturing of biotherapeutics journal December 2020
High cell density fermentation via a metabolically engineered Escherichia coli for the enhanced production of succinic acid journal March 2011
Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure journal April 1995
An efficient succinic acid production process in a metabolically engineered Corynebacterium glutamicum strain journal September 2008
Glycerol/Glucose Co-Fermentation: One More Proficient Process to Produce Propionic Acid by Propionibacterium acidipropionici journal June 2010
Multiple crystallization as a potential strategy for efficient recovery of succinic acid following fermentation with immobilized cells journal February 2020
Engineering microbial factories for synthesis of value-added products journal April 2011
A novel riboregulator switch system of gene expression for enhanced microbial production of succinic acid journal April 2018
Bioprocess development using organic biowaste and sustainability assessment of succinic acid production with engineered Yarrowia lipolytica strain journal October 2021
Techno-economic analysis of succinic acid production using adsorption from fermentation medium journal September 2013
Development and validation of a technoeconomic analysis tool for early-stage evaluation of bio-based chemical production processes journal December 2013
Construction of reductive pathway in Saccharomyces cerevisiae for effective succinic acid fermentation at low pH value journal March 2014
n-Butanol production from sucrose and sugarcane juice by engineered Clostridium tyrobutyricum overexpressing sucrose catabolism genes and adhE2 journal June 2017
Green and sustainable succinic acid production from crude glycerol by engineered Yarrowia lipolytica via agricultural residue based in situ fibrous bed bioreactor journal February 2018
Feasibility of commercial waste biorefineries for cassava starch industries: Techno-economic assessment journal February 2020
Process optimisation for production and recovery of succinic acid using xylose-rich hydrolysates by Actinobacillus succinogenes journal January 2022
Techno-economic evaluation and life cycle assessment of a biorefinery using winery waste streams for the production of succinic acid and value-added co-products journal March 2022
Biorefinery development, techno-economic evaluation and environmental impact analysis for the conversion of the organic fraction of municipal solid waste into succinic acid and value-added fractions journal June 2022
Towards large scale fermentative production of succinic acid journal December 2014
Production of succinic acid by metabolically engineered microorganisms journal December 2016
A comparative study of ethanol production by Issatchenkia orientalis strains under stress conditions journal January 2012
Manipulating pyruvate to acetyl-CoA conversion in Escherichia coli for anaerobic succinate biosynthesis from glucose with the yield close to the stoichiometric maximum journal November 2015
Sustainable production and purification of succinic acid: A review of membrane-integrated green approach journal December 2020
Direct production of fatty alcohols from glucose using engineered strains of Yarrowia lipolytica journal June 2020
Genome-scale metabolic reconstruction of the non-model yeast Issatchenkia orientalis SD108 and its application to organic acids production journal December 2020
Recovery of succinic acid from fermentation broth by forward osmosis-assisted crystallization process journal August 2019
One step recovery of succinic acid from fermentation broths by crystallization journal May 2010
Downstream separation and purification of succinic acid from fermentation broths using spent sulphite liquor as feedstock journal January 2019
Towards the exploitation of glycerol's high reducing power in Saccharomyces cerevisiae-based bioprocesses journal November 2016
Engineering of unconventional yeast Yarrowia lipolytica for efficient succinic acid production from glycerol at low pH journal July 2017
Recent advances in metabolic engineering of Saccharomyces cerevisiae: New tools and their applications journal November 2018
A genetic toolbox for metabolic engineering of Issatchenkia orientalis journal May 2020
Peak Annotation and Verification Engine for Untargeted LC–MS Metabolomics journal December 2018
Metabolic Engineering: Methodologies and Applications journal December 2022
Economic and Environmental Assessment of Succinic Acid Production from Sugarcane Bagasse journal September 2021
Sustainable Production of Acrylic Acid via 3-Hydroxypropionic Acid from Lignocellulosic Biomass journal November 2021
Post-Fermentation Recovery of Biobased Carboxylic Acids journal October 2018
BioSTEAM: A Fast and Flexible Platform for the Design, Simulation, and Techno-Economic Analysis of Biorefineries under Uncertainty journal January 2020
Enzymatic assembly of DNA molecules up to several hundred kilobases journal April 2009
Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase journal April 2020
Glucose repression can be alleviated by reducing glucose phosphorylation rate in Saccharomyces cerevisiae journal February 2018
Sustainable bio-succinic acid production: superstructure optimization, techno-economic, and lifecycle assessment journal January 2021
Novel resin-based vacuum distillation-crystallisation method for recovery of succinic acid crystals from fermentation broths journal January 2010
Engineering energetically efficient transport of dicarboxylic acids in yeast Saccharomyces cerevisiae journal August 2019
INCA: a computational platform for isotopically non-stationary metabolic flux analysis journal January 2014
Engineering robust microorganisms for organic acid production journal September 2021
DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways journal December 2008
Characterization of JEN family carboxylate transporters from the acid‐tolerant yeast Pichia kudriavzevii and their applications in succinic acid production journal February 2021
Metabolic engineering of sugarcane to accumulate energy-dense triacylglycerols in vegetative biomass journal June 2015
Toward Homosuccinate Fermentation: Metabolic Engineering of Corynebacterium glutamicum for Anaerobic Production of Succinate from Glucose and Formate journal May 2012
Development of a CRISPR/Cas9-Based Tool for Gene Deletion in Issatchenkia orientalis journal June 2019
Exploiting Issatchenkia orientalis SD108 for succinic acid production journal August 2014
Toward glycerol biorefinery: metabolic engineering for the production of biofuels and chemicals from glycerol journal October 2016
Efficient metabolic evolution of engineered Yarrowia lipolytica for succinic acid production using a glucose-based medium in an in situ fibrous bioreactor under low-pH condition journal August 2018
Engineering of Yarrowia lipolytica transporters for high-efficient production of biobased succinic acid from glucose journal June 2021
A One Pot, One Step, Precision Cloning Method with High Throughput Capability journal November 2008
Population genomics shows no distinction between pathogenic Candida krusei and environmental Pichia kudriavzevii: One species, four names journal July 2018
Life-cycle Analysis of Bioproducts and Their Conventional Counterparts in GREET report September 2015
Recovery Processes of Organic Acids from Fermentation Broths in the Biomass-Based Industry journal January 2016