Carboxylic Acid Production

A special issue of Fermentation (ISSN 2311-5637). This special issue belongs to the section "Industrial Fermentation".

Deadline for manuscript submissions: closed (31 May 2017) | Viewed by 172147

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Department of Chemical Engineering, Lund University, Lund, Sweden
Interests: biorefineries; yeast; lignocellulose; fermentation technology
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Dear Colleagues,

Carboxylic acids are truly central compounds in cellular metabolism. Carbon dioxide is captured from the atmosphere through formation of carboxylic groups and is also released, in part, by decarboxylation reactions. The reactivity of the carboxylic group with amino- or hydroxyl-groups enables the formation of peptide and ester bonds. The functionality of the carboxylic group is also of huge importance in our industrial world for a wide range of applications. The loosely bound hydrogen provides weak acid functionality, much desired for food industry applications in preservatives and flavour compounds. Citric acid is one of our oldest industrial fermentation products. The presence of two carboxylic groups, or a combination of one carboxylic group and another functional group, make the compounds interesting building blocks for polymer production. A number of carboxylic acids, including, e.g., lactic, succinic, 3-hydroxypropionic and itaconic acids, have been identified and recognized as suitable platform chemicals for a foreseen growing carbohydrate based economy. Economic margins are, however, tight when competing with petroleum based production, and production strains, fermentation technology and—not least—downstream processing, all need to be improved to enable viable commercial production.

This Special issue will cover current developments within this exciting field. Topics will include: Fermentation physiology of natural carboxylic acid producers; screening and isolation of novel producers; metabolic engineering for improving intrinsic carboxylic acid production; metabolic engineering for expanding product range to non-endogenous carboxylic acids; production from lignocellulosic derived sugars or by-product streams; downstream processing for recovery of carboxylic acids; bioprocess design—including continuous processes and integration.
All production organisms—fungi, yeasts, bacteria—are welcome.

Prof. Dr. Gunnar Lidén
Guest Editor

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Keywords

  • fermentation physiology
  • metabolic engineering
  • strain evolution
  • downstream processing
  • bioprocess design

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Published Papers (12 papers)

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Editorial

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175 KiB  
Editorial
Carboxylic Acid Production
by Gunnar Lidén
Fermentation 2017, 3(3), 46; https://doi.org/10.3390/fermentation3030046 - 14 Sep 2017
Cited by 8 | Viewed by 6569
Abstract
Carboxylic acids are central compounds in cellular metabolism, and in the carbon cycle in nature.[...] Full article
(This article belongs to the Special Issue Carboxylic Acid Production)

Research

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5915 KiB  
Article
Biotechnological Production of Fumaric Acid: The Effect of Morphology of Rhizopus arrhizus NRRL 2582
by Aikaterini Papadaki, Nikolaos Androutsopoulos, Maria Patsalou, Michalis Koutinas, Nikolaos Kopsahelis, Aline Machado de Castro, Seraphim Papanikolaou and Apostolis A. Koutinas
Fermentation 2017, 3(3), 33; https://doi.org/10.3390/fermentation3030033 - 8 Jul 2017
Cited by 30 | Viewed by 6726
Abstract
Fumaric acid is a platform chemical with many applications in bio-based chemical and polymer production. Fungal cell morphology is an important factor that affects fumaric acid production via fermentation. In the present study, pellet and dispersed mycelia morphology of Rhizopus arrhizus NRRL 2582 [...] Read more.
Fumaric acid is a platform chemical with many applications in bio-based chemical and polymer production. Fungal cell morphology is an important factor that affects fumaric acid production via fermentation. In the present study, pellet and dispersed mycelia morphology of Rhizopus arrhizus NRRL 2582 was analysed using image analysis software and the impact on fumaric acid production was evaluated. Batch experiments were carried out in shake flasks using glucose as carbon source. The highest fumaric acid yield of 0.84 g/g total sugars was achieved in the case of dispersed mycelia with a final fumaric acid concentration of 19.7 g/L. The fumaric acid production was also evaluated using a nutrient rich feedstock obtained from soybean cake, as substitute of the commercial nitrogen sources. Solid state fermentation was performed in order to produce proteolytic enzymes, which were utilised for soybean cake hydrolysis. Batch fermentations were conducted using 50 g/L glucose and soybean cake hydrolysate achieving up to 33 g/L fumaric acid concentration. To the best of our knowledge the influence of R. arrhizus morphology on fumaric acid production has not been reported previously. The results indicated that dispersed clumps were more effective in fumaric acid production than pellets and renewable resources could be alternatively valorised for the biotechnological production of platform chemicals. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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1090 KiB  
Article
Wheat and Sugar Beet Coproducts for the Bioproduction of 3-Hydroxypropionic Acid by Lactobacillus reuteri DSM17938
by Julien Couvreur, Andreia R. S. Teixeira, Florent Allais, Henry-Eric Spinnler, Claire Saulou-Bérion and Tiphaine Clément
Fermentation 2017, 3(3), 32; https://doi.org/10.3390/fermentation3030032 - 6 Jul 2017
Cited by 11 | Viewed by 6626
Abstract
An experimental design based on Response Surface Methodology (RSM) was used for the formulation of a growth medium based on sugar beet and wheat processing coproducts adapted to the cultivation of Lactobacillus reuteri (L. reuteri) DSM17938. The strain was cultivated on [...] Read more.
An experimental design based on Response Surface Methodology (RSM) was used for the formulation of a growth medium based on sugar beet and wheat processing coproducts adapted to the cultivation of Lactobacillus reuteri (L. reuteri) DSM17938. The strain was cultivated on 30 different media varying by the proportions of sugar beet and wheat processing coproducts, and the concentration of yeast extract, tween 80 and vitamin B12. The media were used in a two-step process consisting of L. reuteri cultivation followed by the bioconversion of glycerol into 3-hydroxypropionic acid by resting cells. The efficiency of the formulations was evaluated according to the maximal optical density at the end of the growth phase (ΔOD620nm) and the ability of the resting cells to convert glycerol into 3-hydroxypropionic acid, a platform molecule of interest for the plastic industry. De Man, Rogosa, and Sharpe medium (MRS), commonly used for the cultivation of lactic bacteria, was used as the control medium. The optimized formulation allowed increasing the 3-HP production. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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829 KiB  
Article
Direct Succinic Acid Production from Minimally Pretreated Biomass Using Sequential Solid-State and Slurry Fermentation with Mixed Fungal Cultures
by Jerico Alcantara, Andro Mondala, Logan Hughey and Shaun Shields
Fermentation 2017, 3(3), 30; https://doi.org/10.3390/fermentation3030030 - 30 Jun 2017
Cited by 25 | Viewed by 8516
Abstract
Conventional bio-based succinic acid production involves anaerobic bacterial fermentation of pure sugars. This study explored a new route for directly producing succinic acid from minimally-pretreated lignocellulosic biomass via a consolidated bioprocessing technology employing a mixed lignocellulolytic and acidogenic fungal co-culture. The process involved [...] Read more.
Conventional bio-based succinic acid production involves anaerobic bacterial fermentation of pure sugars. This study explored a new route for directly producing succinic acid from minimally-pretreated lignocellulosic biomass via a consolidated bioprocessing technology employing a mixed lignocellulolytic and acidogenic fungal co-culture. The process involved a solid-state pre-fermentation stage followed by a two-phase slurry fermentation stage. During the solid-state pre-fermentation stage, Aspergillus niger and Trichoderma reesei were co-cultured in a nitrogen-rich substrate (e.g., soybean hull) to induce cellulolytic enzyme activity. The ligninolytic fungus Phanerochaete chrysosporium was grown separately on carbon-rich birch wood chips to induce ligninolytic enzymes, rendering the biomass more susceptible to cellulase attack. The solid-state pre-cultures were then combined in a slurry fermentation culture to achieve simultaneous enzymatic cellulolysis and succinic acid production. This approach generated succinic acid at maximum titers of 32.43 g/L after 72 h of batch slurry fermentation (~10 g/L production), and 61.12 g/L after 36 h of addition of fresh birch wood chips at the onset of the slurry fermentation stage (~26 g/L production). Based on this result, this approach is a promising alternative to current bacterial succinic acid production due to its minimal substrate pretreatment requirements, which could reduce production costs. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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1375 KiB  
Article
Valorization of a Pulp Industry By-Product through the Production of Short-Chain Organic Acids
by Diogo Queirós, Rita Sousa, Susana Pereira and Luísa S. Serafim
Fermentation 2017, 3(2), 20; https://doi.org/10.3390/fermentation3020020 - 12 May 2017
Cited by 17 | Viewed by 5146
Abstract
In this work, hardwood sulfite spent liquor (HSSL)—a by-product from a pulp and paper industry—was used as substrate to produce short-chain organic acids (SCOAs) through acidogenic fermentation. SCOAs have a broad range of applications, including the production of biopolymers, bioenergy, and biological removal [...] Read more.
In this work, hardwood sulfite spent liquor (HSSL)—a by-product from a pulp and paper industry—was used as substrate to produce short-chain organic acids (SCOAs) through acidogenic fermentation. SCOAs have a broad range of applications, including the production of biopolymers, bioenergy, and biological removal of nutrients from wastewaters. A continuous stirred tank reactor (CSTR) configuration was chosen to impose selective pressure conditions. The CSTR was operated for 88 days at 30 °C, without pH control, and 1.76 days of hydraulic and sludge retention times were imposed. The culture required 46 days to adapt to the conditions imposed, reaching a pseudo-steady state after this period. The maximum concentration of SCOAs produced occurred on day 71—7.0 g carbon oxygen demand (COD)/L that corresponded to a degree of acidification of 36%. Acetate, propionate, butyrate, valerate, and lactate were the SCOAs produced throughout the 88 days, with an average proportion of 59:17:19:1.0:4.0%, respectively. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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1569 KiB  
Article
Purification of Polymer-Grade Fumaric Acid from Fermented Spent Sulfite Liquor
by Diogo Figueira, João Cavalheiro and Bruno Sommer Ferreira
Fermentation 2017, 3(2), 13; https://doi.org/10.3390/fermentation3020013 - 1 Apr 2017
Cited by 12 | Viewed by 7674
Abstract
Fumaric acid is a chemical building block with many applications, namely in the polymer industry. The fermentative production of fumaric acid from renewable feedstock is a promising and sustainable alternative to petroleum-based chemical synthesis. The use of existing industrial side-streams as raw-materials within [...] Read more.
Fumaric acid is a chemical building block with many applications, namely in the polymer industry. The fermentative production of fumaric acid from renewable feedstock is a promising and sustainable alternative to petroleum-based chemical synthesis. The use of existing industrial side-streams as raw-materials within biorefineries potentially enables production costs competitive against current chemical processes, while preventing the use of refined sugars competing with food and feed uses and avoiding purposely grown crops requiring large areas of arable land. However, most industrial side streams contain a diversity of molecules that will add complexity to the purification of fumaric acid from the fermentation broth. A process for the recovery and purification of fumaric acid from a complex fermentation medium containing spent sulfite liquor (SSL) as a carbon source was developed and is herein described. A simple two-stage precipitation procedure, involving separation unit operations, pH and temperature manipulation and polishing through the removal of contaminants with activated carbon, allowed for the recovery of fumaric acid with 68.3% recovery yield with specifications meeting the requirements of the polymer industry. Further, process integration opportunities were implemented that allowed minimizing the generation of waste streams containing fumaric acid, which enabled increasing the yield to 81.4% while keeping the product specifications. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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1043 KiB  
Article
Mixed Carboxylic Acid Production by Megasphaera elsdenii from Glucose and Lignocellulosic Hydrolysate
by Robert S. Nelson, Darren J. Peterson, Eric M. Karp, Gregg T. Beckham and Davinia Salvachúa
Fermentation 2017, 3(1), 10; https://doi.org/10.3390/fermentation3010010 - 1 Mar 2017
Cited by 56 | Viewed by 11430
Abstract
Volatile fatty acids (VFAs) can be readily produced from many anaerobic microbes and subsequently utilized as precursors to renewable biofuels and biochemicals. Megasphaera elsdenii represents a promising host for production of VFAs, butyric acid (BA) and hexanoic acid (HA). However, due to the [...] Read more.
Volatile fatty acids (VFAs) can be readily produced from many anaerobic microbes and subsequently utilized as precursors to renewable biofuels and biochemicals. Megasphaera elsdenii represents a promising host for production of VFAs, butyric acid (BA) and hexanoic acid (HA). However, due to the toxicity of these acids, product removal via an extractive fermentation system is required to achieve high titers and productivities. Here, we examine multiple aspects of extractive separations to produce BA and HA from glucose and lignocellulosic hydrolysate with M. elsdenii. A mixture of oleyl alcohol and 10% (v/v) trioctylamine was selected as an extraction solvent due to its insignificant inhibitory effect on the bacteria. Batch extractive fermentations were conducted in the pH range of 5.0 to 6.5 to select the best cell growth rate and extraction efficiency combination. Subsequently, fed-batch pertractive fermentations were run over 230 h, demonstrating high BA and HA concentrations in the extracted fraction (57.2 g/L from ~190 g/L glucose) and productivity (0.26 g/L/h). To our knowledge, these are the highest combined acid titers and productivity values reported for M. elsdenii and bacterial mono-cultures from sugars. Lastly, the production of BA and HA (up to 17 g/L) from lignocellulosic sugars was demonstrated. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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Review

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531 KiB  
Review
Succinic Acid: Technology Development and Commercialization
by Nhuan P. Nghiem, Susanne Kleff and Stefan Schwegmann
Fermentation 2017, 3(2), 26; https://doi.org/10.3390/fermentation3020026 - 9 Jun 2017
Cited by 186 | Viewed by 30834
Abstract
Succinic acid is a precursor of many important, large-volume industrial chemicals and consumer products. It was once common knowledge that many ruminant microorganisms accumulated succinic acid under anaerobic conditions. However, it was not until the discovery of Anaerobiospirillum succiniciproducens at the Michigan Biotechnology [...] Read more.
Succinic acid is a precursor of many important, large-volume industrial chemicals and consumer products. It was once common knowledge that many ruminant microorganisms accumulated succinic acid under anaerobic conditions. However, it was not until the discovery of Anaerobiospirillum succiniciproducens at the Michigan Biotechnology Institute (MBI), which was capable of producing succinic acid up to about 50 g/L under optimum conditions, that the commercial feasibility of producing the compound by biological processes was realized. Other microbial strains capable of producing succinic acid to high final concentrations subsequently were isolated and engineered, followed by development of fermentation processes for their uses. Processes for recovery and purification of succinic acid from fermentation broths were simultaneously established along with new applications of succinic acid, e.g., production of biodegradable deicing compounds and solvents. Several technologies for the fermentation-based production of succinic acid and the subsequent conversion to useful products are currently commercialized. This review gives a summary of the development of microbial strains, their fermentation, and the importance of the down-stream recovery and purification efforts to suit various applications in the context of their current commercialization status for biologically derived succinic acid. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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1179 KiB  
Review
Biochemical Production and Separation of Carboxylic Acids for Biorefinery Applications
by Nanditha Murali, Keerthi Srinivas and Birgitte K. Ahring
Fermentation 2017, 3(2), 22; https://doi.org/10.3390/fermentation3020022 - 19 May 2017
Cited by 88 | Viewed by 15296
Abstract
Carboxylic acids are traditionally produced from fossil fuels and have significant applications in the chemical, pharmaceutical, food, and fuel industries. Significant progress has been made in replacing such fossil fuel sources used for production of carboxylic acids with sustainable and renewable biomass resources. [...] Read more.
Carboxylic acids are traditionally produced from fossil fuels and have significant applications in the chemical, pharmaceutical, food, and fuel industries. Significant progress has been made in replacing such fossil fuel sources used for production of carboxylic acids with sustainable and renewable biomass resources. However, the merits and demerits of each carboxylic acid processing platform are dependent on the application of the final product in the industry. There are a number of studies that indicate that separation processes account for over 30% of the total processing costs in such processes. This review focuses on the sustainable processing of biomass resources to produce carboxylic acids. The primary focus of the review will be on a discussion of and comparison between existing biochemical processes for producing lower-chain fatty acids such as acetic-, propionic-, butyric-, and lactic acids. The significance of these acids stems from the recent progress in catalytic upgrading to produce biofuels apart from the current applications of the carboxylic acids in the food, pharmaceutical, and plastics sectors. A significant part of the review will discuss current state-of-art of techniques for separation and purification of these acids from fermentation broths for further downstream processing to produce high-value products. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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366 KiB  
Review
Microbial Propionic Acid Production
by R. Axayacatl Gonzalez-Garcia, Tim McCubbin, Laura Navone, Chris Stowers, Lars K. Nielsen and Esteban Marcellin
Fermentation 2017, 3(2), 21; https://doi.org/10.3390/fermentation3020021 - 15 May 2017
Cited by 189 | Viewed by 42401
Abstract
Propionic acid (propionate) is a commercially valuable carboxylic acid produced through microbial fermentation. Propionic acid is mainly used in the food industry but has recently found applications in the cosmetic, plastics and pharmaceutical industries. Propionate can be produced via various metabolic pathways, which [...] Read more.
Propionic acid (propionate) is a commercially valuable carboxylic acid produced through microbial fermentation. Propionic acid is mainly used in the food industry but has recently found applications in the cosmetic, plastics and pharmaceutical industries. Propionate can be produced via various metabolic pathways, which can be classified into three major groups: fermentative pathways, biosynthetic pathways, and amino acid catabolic pathways. The current review provides an in-depth description of the major metabolic routes for propionate production from an energy optimization perspective. Biological propionate production is limited by high downstream purification costs which can be addressed if the target yield, productivity and titre can be achieved. Genome shuffling combined with high throughput omics and metabolic engineering is providing new opportunities, and biological propionate production is likely to enter the market in the not so distant future. In order to realise the full potential of metabolic engineering and heterologous expression, however, a greater understanding of metabolic capabilities of the native producers, the fittest producers, is required. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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404 KiB  
Review
Microbial Production of Malic Acid from Biofuel-Related Coproducts and Biomass
by Thomas P. West
Fermentation 2017, 3(2), 14; https://doi.org/10.3390/fermentation3020014 - 10 Apr 2017
Cited by 44 | Viewed by 14161
Abstract
The dicarboxylic acid malic acid synthesized as part of the tricarboxylic acid cycle can be produced in excess by certain microorganisms. Although malic acid is produced industrially to a lesser extent than citric acid, malic acid has industrial applications in foods and pharmaceuticals [...] Read more.
The dicarboxylic acid malic acid synthesized as part of the tricarboxylic acid cycle can be produced in excess by certain microorganisms. Although malic acid is produced industrially to a lesser extent than citric acid, malic acid has industrial applications in foods and pharmaceuticals as an acidulant among other uses. Only recently has the production of this organic acid from coproducts of industrial bioprocessing been investigated. It has been shown that malic acid can be synthesized by microbes from coproducts generated during biofuel production. More specifically, malic acid has been shown to be synthesized by species of the fungus Aspergillus on thin stillage, a coproduct from corn-based ethanol production, and on crude glycerol, a coproduct from biodiesel production. In addition, the fungus Ustilago trichophora has also been shown to produce malic acid from crude glycerol. With respect to bacteria, a strain of the thermophilic actinobacterium Thermobifida fusca has been shown to produce malic acid from cellulose and treated lignocellulosic biomass. An alternate method of producing malic acid is to use agricultural biomass converted to syngas or biooil as a substrate for fungal bioconversion. Production of poly(β-l-malic acid) by strains of Aureobasidium pullulans from agricultural biomass has been reported where the polymalic acid is subsequently hydrolyzed to malic acid. This review examines applications of malic acid, metabolic pathways that synthesize malic acid and microbial malic acid production from biofuel-related coproducts, lignocellulosic biomass and poly(β-l-malic acid). Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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475 KiB  
Review
Recent Progress in the Microbial Production of Pyruvic Acid
by Neda Maleki and Mark A. Eiteman
Fermentation 2017, 3(1), 8; https://doi.org/10.3390/fermentation3010008 - 13 Feb 2017
Cited by 52 | Viewed by 14005
Abstract
Pyruvic acid (pyruvate) is a cellular metabolite found at the biochemical junction of glycolysis and the tricarboxylic acid cycle. Pyruvate is used in food, cosmetics, pharmaceutical and agricultural applications. Microbial production of pyruvate from either yeast or bacteria relies on restricting the natural [...] Read more.
Pyruvic acid (pyruvate) is a cellular metabolite found at the biochemical junction of glycolysis and the tricarboxylic acid cycle. Pyruvate is used in food, cosmetics, pharmaceutical and agricultural applications. Microbial production of pyruvate from either yeast or bacteria relies on restricting the natural catabolism of pyruvate, while also limiting the accumulation of the numerous potential by-products. In this review we describe research to improve pyruvate formation which has targeted both strain development and process development. Strain development requires an understanding of carbohydrate metabolism and the many competing enzymes which use pyruvate as a substrate, and it often combines classical mutation/isolation approaches with modern metabolic engineering strategies. Process development requires an understanding of operational modes and their differing effects on microbial growth and product formation. Full article
(This article belongs to the Special Issue Carboxylic Acid Production)
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