☆ 4.8 Review

Microbial itaconic acid bioproduction towards sustainable development: Insights, challenges, and prospects

BIORESOURCE TECHNOLOGY (2023)

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Role of microalgae in achieving sustainable development goals and circular economy

A. G. Olabi et al.

Summary: In 2015, the United Nations set 17 Sustainable Development Goals to be achieved by 2030, including addressing climate change and creating sustainable industries, jobs, and communities. Microalgae, due to their ability to consume CO2 and their diverse applications in various sectors, play a significant role in achieving these goals. This study discusses the roles of microalgae in achieving the SDGs and their contribution to the circular economy.

SCIENCE OF THE TOTAL ENVIRONMENT (2023)

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Article Biotechnology & Applied Microbiology

High-level itaconic acid (IA) production using engineered Escherichia coli Lemo21(DE3) toward sustainable biorefinery

Priskila Adjani Diankristanti et al.

Summary: Using whole-cell biocatalysts to produce itaconic acid (IA) from citrate is an alternative approach to overcome the limitations of in vivo IA production. By employing engineered E.coli Lemo21(DE3) with aconitase (Acn) and cis-aconitate decarboxylase (CadA), IA titer of 72.44 g/L was achieved, which increased to 81.6 g/L after cold-treating the biocatalysts. Furthermore, a new seeding strategy in Terrific Broth (TB) maintained the biocatalysts stability for up to 30 days and the highest IA titer of 98.17 g/L was obtained using the L21::7G chassis.

ENZYME AND MICROBIAL TECHNOLOGY (2023)

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Article Biotechnology & Applied Microbiology

Alleviating glucose repression and enhancing respiratory capacity to increase itaconic acid production

Yaying Xu et al.

Summary: This study aimed to improve itaconic acid (IA) production in Saccha-romyces cerevisiae by increasing gene expressions related to glucose derepression without impairing yeast growth on glucose. Engineering the acetyl-CoA synthesis pathway increased the titer of IA, and knocking out a negative regulator of the mitochondrial retrograde signaling further increased IA production.

SYNTHETIC AND SYSTEMS BIOTECHNOLOGY (2023)

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Review Agricultural Engineering

Recent advances in lignocellulosic biomass for biofuels and value-added bioproducts-A critical review

Veeramuthu Ashokkumar et al.

Summary: Lignocellulosic biomass is a renewable, economical, and carbon-neutral feedstock, but its complex multi-scale structure poses challenges for valorization and saccharification. This review discusses the latest methods and technologies in biomass pretreatment, as well as genetic engineering techniques for developing advanced strategies in fermentation processes. The aim is to bridge the gap in developing economically feasible lignocellulosic products and chemicals using biorefining technologies.

BIORESOURCE TECHNOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Effective whole cell biotransformation of arginine to a four-carbon diamine putrescine using engineered Escherichia coli

Shih-Chen Yang et al.

Summary: The demand for bio-based materials to replace traditional plastics is growing. In this study, a time-efficient method was developed to convert L-arginine into putrescine using whole cell bioconversion. It was found that the key enzymes from different combinations of plasmids can effectively collaborate, achieving a high conversion rate.

BIOCHEMICAL ENGINEERING JOURNAL (2022)

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Review Agricultural Engineering

Recent advances in the development of Aspergillus for protein production

Qinghua Li et al.

Summary: Aspergillus has been widely used in industrial production of recombinant proteins due to its safety, broad substrate utilization spectrum, efficient post-translational modification, and strong protein secretion capacity. However, challenges in genetic manipulation and varying expression levels of heterologous proteins have hindered its further development and application. Recent advances in CRISPR genome editing and high-throughput screening platforms have facilitated modifications and applications of Aspergillus. Multi-omics analysis and multiplexed genetic engineering have also promoted effective knowledge mining.

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Article Agricultural Engineering

Combinatorial metabolic engineering of Escherichia coli for de novo production of 2′-fucosyllactose

Lu Lin et al.

Summary: In this study, the production of 2'-FL was increased through metabolic engineering. By increasing the gene copies of FutC and deleting multiple genes in competitive pathways, the titer of 2'-FL was raised to 3.3 g/L and reached 10.3 g/L in a large-scale fermentation.

BIORESOURCE TECHNOLOGY (2022)

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Article Agricultural Engineering

Acetate-based production of itaconic acid with Corynebacterium glutamicum using an integrated pH-coupled feeding control

Manuel Merkel et al.

Summary: To date, most bio-based products of industrial biotechnology are derived from sugar-based carbon sources, which compete with food and feed resources. In this study, an engineered strain of Corynebacterium glutamicum ATCC 13032 was used to produce itaconic acid from acetate, overcoming current production challenges. The results show the potential of using acetate as an alternative substrate for bioproduction, with a high peak volumetric productivity and itaconate titer achieved.

BIORESOURCE TECHNOLOGY (2022)

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Article Agriculture, Dairy & Animal Science

Effects of dietary supplementation with itaconic acid on the growth performance, nutrient digestibility, slaughter variables, blood biochemical parameters, and intestinal morphology of broiler chickens

Xin Zhu et al.

Summary: The study found that dietary supplementation of 0.4% itaconic acid (IA) can improve nutrient digestibility, slaughter performance, antioxidant ability, and intestinal morphology of broiler chickens.

POULTRY SCIENCE (2022)

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Article Biochemical Research Methods

Photocontrol of Itaconic Acid Synthesis in Escherichia coli

Yuting Li et al.

Summary: Metabolic engineering has developed a new strategy to enhance itaconic acid production by using light-sensitive proteins to regulate metabolic pathways, which can be extended for optimizing and improving the production of other high-value bioengineering chemicals.

ACS SYNTHETIC BIOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Engineering Yarrowia lipolytica to Produce Itaconic Acid From Waste Cooking Oil

Lanxin Rong et al.

Summary: This study developed a microbial cell factory that utilizes waste cooking oil as raw material for the production of itaconic acid. Through gene expression and overexpression, the production yield was significantly improved, achieving a high IA titer in a 5 L bioreactor.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2022)

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Article Biotechnology & Applied Microbiology

A CRISPRi mediated self-inducible system for dynamic regulation of TCA cycle and improvement of itaconic acid production in Escherichia coli

Ming Zhao et al.

Summary: This study developed a CRISPRi-mediated self-inducible system (CiMS) to dynamically regulate the metabolic flux and enhance the production capacity of itaconic acid (ITA) in Escherichia coli. By optimizing the flux distribution, the ITA titer was increased by 23%. The CiMS strategy demonstrated its effectiveness in regulating metabolic flux in microbial cell factories.

SYNTHETIC AND SYSTEMS BIOTECHNOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Construction of cell factory through combinatorial metabolic engineering for efficient production of itaconic acid

Jiao Feng et al.

Summary: In this study, combinatorial engineering strategies were employed to construct efficient Escherichia coli cells for itaconic acid production. By optimizing reaction conditions and implementing feeding control strategies, the highest itaconic acid titer was achieved. Additionally, enzyme evolution and protein scaffold synthesis were utilized to improve the biosynthesis efficiency of itaconic acid.

MICROBIAL CELL FACTORIES (2022)

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Article Polymer Science

Starch and itaconic acid-based superabsorbent hydrogels for agricultural application

Ashok Bora et al.

Summary: This study synthesized a biobased superabsorbent with high water absorption capacity and fast water absorption rate using starch and itaconic acid, which shows great potential to be used as an environmentally friendly superabsorbent in agricultural applications.

EUROPEAN POLYMER JOURNAL (2022)

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Article Biotechnology & Applied Microbiology

Synergistic effects on itaconic acid production in engineered Aspergillus niger expressing the two distinct biosynthesis clusters from Aspergillus terreus and Ustilago maydis

Yaqi Wang et al.

Summary: This study optimized the production of itaconic acid (IA) using A. niger as the chassis. By combining the IA biosynthesis pathways from A. terreus and Ustilago maydis, higher IA titers were achieved. Additionally, increasing the copy number of cadA, blocking IA degradation by deleting ictA, and enhancing the supply of IA precursor by overexpressing acoA all showed positive effects on IA accumulation.

MICROBIAL CELL FACTORIES (2022)

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Itaconic acid production is regulated by LaeA in Aspergillus pseudoterreus

Kyle R. Pomraning et al.

Summary: The global regulator LaeA plays a crucial role in controlling secondary metabolism in diverse Aspergillus species. This study reveals its importance in regulating itaconic acid production in Aspergillus pseudoterreus. Overexpression of LaeA enhances itaconic acid yield by increasing the expression of key biosynthetic pathway enzymes and attenuating the expression of genes involved in phosphate acquisition and scavenging.

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Recent advances and challenges in the bioconversion of acetate to value-added chemicals

Sakuntala Mutyala et al.

Summary: Acetate, a major byproduct of bioconversion, has the potential to produce various high-value platform chemicals and biofuels, but yields and titers have not reached their maximum. Recombinant strain development and pathway regulation are suggested to overcome this limitation.

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Article Biotechnology & Applied Microbiology

Tailoring key enzymes for renewable and high-level itaconic acid production using genetic Escherichia coli via whole-cell bioconversion

Chuan-Chieh Hsiang et al.

Summary: Renewable chemical production through carbon-neutral design has received significant attention. In this study, the WC bioconversion of citrate into IA using key enzymes ACN and CAD showed promising results, with CAD identified as the rate-determining step. Metal ions like copper and ferric ions were found to inhibit enzyme activity when both enzymes co-worked. The engineered E. coli expressing dual genes achieved a high IA titer and productivity, demonstrating a promising renewable process.

ENZYME AND MICROBIAL TECHNOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Metabolic engineering of Schizosaccharomyces pombe for itaconic acid production

Naofumi Fujie et al.

Summary: This study developed a metabolic engineering strategy to produce Itaconic acid (IA) from glucose in the fission yeast Schizosaccharomyces pombe. Through heterologous expression of the CAD gene and mitochondrial localization, as well as the construction of mutant strains, the production of IA was significantly increased.

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Article Biotechnology & Applied Microbiology

Enzyme activity engineering based on sequence co-evolution analysis

Donghyo Kim et al.

Summary: The utility of engineering enzyme activity is expanding as biotechnology develops. Traditional methods have limited applicability, but a strategy called sequence co-evolutionary analysis has been developed to improve enzyme activity and control reaction efficiency. This strategy has successfully predicted enzyme activities and controlled the activities of different enzymes in chemical production.

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Article Multidisciplinary Sciences

Kinetic compartmentalization by unnatural reaction for itaconate production

Dae-yeol Ye et al.

Summary: Unlike eukaryotic systems, bacterial hosts lack a membranous system, which is a limitation for efficient metabolic engineering. In this study, a kinetic compartmentalization strategy was used to increase substrate availability from competitive reactions for the efficient production of itaconate in E. coli.

NATURE COMMUNICATIONS (2022)

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Review Biotechnology & Applied Microbiology

From Acetate to Bio-Based Products: Underexploited Potential for Industrial Biotechnology

Dirk Kiefer et al.

Summary: Acetate, as a promising alternative carbon source that may be generated from lignocellulosic biomass and C1 gases in substantial amounts, is discussed in this review as a next-generation platform substrate in industrial biotechnology. The review also highlights alternative sources and routes for acetate production, as well as the biotechnological aspects of microbial acetate utilization and conversion into value-added bioproducts.

TRENDS IN BIOTECHNOLOGY (2021)

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Review Biotechnology & Applied Microbiology

Recent advances in itaconic acid production from microbial cell factories

Deeksha Gopaliya et al.

Summary: Itaconic acid is a versatile molecule with a wide range of applications, which can be produced through both chemical and biological routes. Although Aspergillus terreus is a prevalent microbial cell factory for itaconic acid production, high manufacturing costs remain a challenge. To enable wider applications, a low-cost production process and improved strain performance are essential.

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Microbial itaconic acid production from starchy food waste by newly isolated thermotolerant Aspergillus terreus strain

Vivek Narisetty et al.

Summary: The newly isolated Aspergillus terreus BD strain showed the potential to accumulate itaconic acid at higher temperature. By optimizing the medium, the IA accumulation reached 28.9 g/L. The enzymatic saccharification of synthetic food waste was optimized to achieve a maximum glucose release of 0.60 g/g.

BIORESOURCE TECHNOLOGY (2021)

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Gene expression regulates metabolite homeostasis during the Crabtree effect: Implications for the adaptation and evolution of Metabolism

Douglas L. Rothman et al.

Summary: Research indicates that during the Crabtree effect in yeast, short-term adaptation depends on the ability of the glycogen/trehalose shunt to balance the glycolytic pathway, with later gene expression of new isoforms of glycolytic enzymes providing additional homeostatic mechanisms for increased ATP production and product efficiency while maintaining glycolytic balance.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Migration of glutamate decarboxylase by cold treatment on whole-cell biocatalyst triggered activity for 4-aminobutyric acid production in engineering Escherichia coli

Chengfeng Xue et al.

Summary: By overexpressing GadB in Escherichia coli and subjecting it to cold treatment, the enzymatic turnover rate and migration rate of GadB increased, leading to improved GABA production in whole-cell biotransformation.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2021)

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Incorporation of Poly(Itaconic Acid) with Quaternized Thiazole Groups on Gelatin-Based Films for Antimicrobial-Active Food Packaging

Celeste Cottet et al.

Summary: The modified polymers were incorporated into gelatin to develop antimicrobial-active films, improving mechanical properties and reducing solution absorption capacity. However, the synthesized polymers increased the deformation at break values and the water vapor permeability of films.

POLYMERS (2021)

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Article Microbiology

An Optimized Ustilago maydis for Itaconic Acid Production at Maximal Theoretical Yield

Johanna Becker et al.

Summary: The study focused on using Ustilago maydis to produce itaconic acid, a potential bio-based building block, through metabolic and morphology engineering. By combining various modifications, the production yield was optimized to the theoretical maximum under biotechnologically relevant fed-batch fermentations.

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Integrated gene engineering synergistically improved substrate-product transport, cofactor generation and gene translation for cadaverine biosynthesis in E. coli

Tolbert Osire et al.

Summary: Various approaches have been explored to efficiently produce cadaverine, a bio-based diaminewith broad industrial applications. By expressing SmcadA in E. coli, addition of mild surfactants, overexpressing antiporter cadB, pyridoxal kinases pdxK and pdxY, and screening synthetic RBS libraries, the biosynthesis of cadaverine was enhanced. Mutants design and molecular dynamics simulations helped understand the mechanisms involved in high cadaverine synthesis.

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Adaptations in metabolism and protein translation give rise to the Crabtree effect in yeast

Carl Malina et al.

Summary: The Crabtree effect, observed in many eukaryotic cells, allows for higher growth rates at high glucose availability. Differences in energy metabolism and protein translation efficiency play a key role in distinguishing between Crabtree-positive and Crabtree-negative yeasts.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Cell Catalysis of Citrate to Itaconate by Engineered Halomonas bluephagenesis

Jing Zhang et al.

Summary: Through genetic engineering, Halomonas bluephagenesis with high tolerance successfully produces high titers of itaconic acid (IA) from citrate using a cell catalytic strategy. Under optimized conditions, the conversion rate reaches 93.24% with a productivity of 1.63 g/(L h).

ACS SYNTHETIC BIOLOGY (2021)

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Review Biotechnology & Applied Microbiology

Insights into the structure of Escherichia coli outer membrane as the target for engineering microbial cell factories

Jianli Wang et al.

Summary: Escherichia coli is commonly used as a model bacteria in defining microbial cell factories and studying regulatory mechanisms. The outer membrane associated molecules such as phospholipids and lipopolysaccharides play important roles in cellular morphology and stress adaptation, but can also lead to contamination and nutrient consumption. Understanding the biosynthesis and functions of these molecules is crucial for improving microbial producers.

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Production of itaconic acid from alkali pretreated lignin by dynamic two stage bioconversion

Joshua R. Elmore et al.

Summary: Expanding lignin-derived product portfolio is crucial for sustainable bio-based economy. Researchers engineered Pseudomonas putida to produce itaconic acid at high yields from lignin-derived compounds. Dynamic metabolic control rerouting carbon in central metabolism enabled high yields of valuable chemicals from lignin.

NATURE COMMUNICATIONS (2021)

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Design and construction of novel biocatalyst for bioprocessing: Recent advances and future outlook

Yameng Xu et al.

Summary: Bioprocess, a biocatalysis-based technology, is popular in research and industrial manufacturing, but faces challenges like low productivity and high costs. Strategies like protein engineering and metabolic engineering have been developed to improve biocatalyst efficiency. Combining protein engineering and metabolic engineering is crucial for efficient biocatalysts.

BIORESOURCE TECHNOLOGY (2021)

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Whole-cell biocatalyst for cadaverine production using stable, constitutive and high expression of lysine decarboxylase in recombinant Escherichia coli W3110

Wan-Wen Ting et al.

Summary: This study established a stable and high-level expression system for CadA production, achieving high productivity and yield of cadaverine in engineered E. coli strain JW. The whole-cell biocatalyst showed excellent reusability and potential for bio-nylon production in the future.

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Itaconic acid exerts anti-inflammatory and antibacterial effects via promoting pentose phosphate pathway to produce ROS

Xiaoyang Zhu et al.

Summary: This study revealed the mechanism of itaconic acid as an anti-inflammatory metabolite and confirmed the inhibition of bacterial pathogens with itaconic acid via ROS in cell.

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Overcoming glutamate auxotrophy in Escherichia coli itaconate overproducer by the Weimberg pathway

Ken W. Lu et al.

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Utilization of ethanol for itaconic acid biosynthesis by engineered Saccharomyces cerevisiae

Yaying Xu et al.

Summary: In Saccharomyces cerevisiae, ethanol can play a dual role in providing both a carbon source and NADH donor for the production of acetyl-CoA derivatives. The study found that mitochondrial membrane transporter proteins and upregulation of AAC2 can enhance itaconic acid production by accelerating ethanol utilization. Additionally, overexpression of AAC2 can increase IA titer by upregulating key pathways in the mitochondrial membrane.

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Utilization of ethanol for itaconic acid biosynthesis by engineered Saccharomyces cerevisiae

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Summary: This study investigated the metabolic regulation of ethanol utilization for itaconic acid production in Saccharomyces cerevisiae, highlighting the importance of mitochondrial membrane transporter proteins in the process. Upregulating the major ADP/ATP carrier AAC2 was found to accelerate ethanol utilization and itaconic acid production. RNA sequencing results indicated that AAC2 overexpression enhanced IA production by upregulating specific pathways in mitochondrial membrane, while exogenous aconitase expression did not increase IA production but affected ethanol utilization and cell growth. Ethanol metabolism in Saccharomyces cerevisiae is closely related to itaconic acid production.

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