Genetic and Process Engineering for the Simultaneous Saccharification and Biocatalytic Conversion of Lignocellulose for Itaconic Acid Production by Myceliophthora thermophila

Itaconic acid (IA), one of the top twelve renewable platform chemicals, is a key precursor for polymer synthesis. Here, we engineered Myceliophthora thermophila for efficient consolidated biocatalytic IA production from lignocellulose by introducing the heterologous IA pathway (cis-aconitic acid decarboxylase (CAD), mitochondrial tricarboxylic transporter (MTT), major facilitator superfamily transporter (MFS) from Aspergillus terreus), and boosting CAD expression and precursor supply. A critical issue was temperature mismatch: optimal fungal growth vs. CAD activity. Transcriptomics analysis identified reduced expression of glycolytic rate-limiting enzymes (fructose-bisphosphate aldolase, FBA; phosphofructokinase, PFK) at 40 °C. Overexpressing these enzymes in strain IA32 generated strain IA41 (with 3.1-fold and 2.8-fold higher expression of pfk and fba, respectively), which accelerated glucose consumption by 53.2% and increased IA yield by 55.1% A two-stage temperature-shift strategy (45 °C for growth/saccharification, 40 °C for CAD activity) was developed. The engineered strain achieved 3.93 g/L IA in shake flasks and 10.51 g/L in corncob fed-batch fermentation—the highest reported titer for consolidated lignocellulose-to-IA processes. This establishes M. thermophila as a robust platform for cost-effective IA production from lignocellulose.

• Publication year

  2025

• Venue

  Catalysts

• Publication date

  2025-11-09

• Fields of study

  Not labeled

• Identifiers
  DOI 10.3390/catal15111066
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Metabolic Engineering of Filamentous Fungus Trichoderma reesei for Itaconic Acid Production

  2025cited by this paper
• Harnessing Synthetic Biology for Sustainable Industrial Innovation: Advances, Challenges, and Future Direction

  2025cited by this paper
• Myceliophthora thermophila as promising fungal cell factories for industrial bioproduction: From rational design to industrial applications.

  2025cited by this paper
• Improved consolidated bioprocessing for itaconic acid production by simultaneous optimization of cellulase and metabolic pathway of Neurospora crassa

  2024influential reference
• Pyrophosphate-free glycolysis in Clostridium thermocellum increases both thermodynamic driving force and ethanol titers

  2024cited by this paper
• Reprogramming Yarrowia lipolytica metabolism for efficient synthesis of itaconic acid from flask to semipilot scale

  2024cited by this paper
• Compartmentalization of a synergistic fungal-bacterial consortium to boost lactic acid conversion from lignocellulose via consolidated bioprocessing

  2023cited by this paper
• Itaconic acid and dimethyl itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle.

  2023cited by this paper
• Lignocellulosic Biorefinery Technologies: A Perception into Recent Advances in Biomass Fractionation, Biorefineries, Economic Hurdles and Market Outlook

  2023cited by this paper
• Effect of itaconic acid production on Neurospora crassa in consolidated bioprocessing of cellulose

  2023cited by this paper
• Recent Advances on the Production of Itaconic Acid via the Fermentation and Metabolic Engineering

  2023influential reference
• Synergistic effects on itaconic acid production in engineered Aspergillus niger expressing the two distinct biosynthesis clusters from Aspergillus terreus and Ustilago maydis

  2022cited by this paper
• Evaluation of Metabolic Engineering Strategies on 2-Ketoisovalerate Production by Escherichia coli

  2022cited by this paper
• A CRISPRi mediated self-inducible system for dynamic regulation of TCA cycle and improvement of itaconic acid production in Escherichia coli

  2022cited by this paper
• Integrated perspective on microbe-based production of itaconic acid: from metabolic and strain engineering to upstream and downstream strategies

  2022cited by this paper
• Designing and Constructing a Novel Artificial Pathway for Malonic Acid Production Biologically

  2022cited by this paper
• Global Status of Lignocellulosic Biorefinery: Challenges and Perspectives.

  2021cited by this paper
• Coordination of consolidated bioprocessing technology and carbon dioxide fixation to produce malic acid directly from plant biomass in Myceliophthora thermophila

  2021cited by this paper
• Influence of the structure and properties of lignocellulose on the physicochemical characteristics of lignocellulose-based residues used as an environmentally friendly substrate.

  2021cited by this paper
• Advances in Valorization of Lignocellulosic Biomass towards Energy Generation

  2021cited by this paper
• Direct production of commodity chemicals from lignocellulose using Myceliophthora thermophila.

  2020influential reference
• Metabolic specialization in itaconic acid production: a tale of two fungi.

  2020cited by this paper
• Itaconic acid derivatives: structure, function, biosynthesis, and perspectives

  2020cited by this paper
• Consolidated production of coniferol and other high-value aromatic alcohols directly from lignocellulosic biomass

  2020cited by this paper
• Efficient ethanol production from paper mulberry pretreated at high solid loading in Fed-nonisothermal-simultaneous saccharification and fermentation

  2020cited by this paper
• Metabolic engineering of an industrial Aspergillus niger strain for itaconic acid production

  2020cited by this paper
• Metabolic engineering with ATP-citrate lyase and nitrogen source supplementation improves itaconic acid production in Aspergillus niger

  2019cited by this paper
• Enhanced itaconic acid production in Yarrowia lipolytica via heterologous expression of a mitochondrial transporter MTT

  2019cited by this paper
• Reflection on the research on and implementation of biorefinery systems – a systematic literature review with a focus on feedstock

  2019cited by this paper
• Manufacturing Multienzymatic Complex Reactors In Vivo by Self-Assembly To Improve the Biosynthesis of Itaconic Acid in Escherichia coli.

  2018cited by this paper
• World market and biotechnological production of itaconic acid

  2018influential reference
• Metabolic engineering of the thermophilic filamentous fungus Myceliophthora thermophila to produce fumaric acid

  2018cited by this paper
• Consolidated bioprocessing of lignocellulosic biomass to itaconic acid by metabolically engineering Neurospora crassa

  2018influential reference
• High oxygen tension increases itaconic acid accumulation, glucose consumption, and the expression and activity of alternative oxidase in Aspergillus terreus

  2018cited by this paper
• Catalytic Transformation of Lignocellulosic Biomass into Arenes, 5-Hydroxymethylfurfural, and Furfural.

  2018cited by this paper
• Production of itaconate by whole-cell bioconversion of citrate mediated by expression of multiple cis-aconitate decarboxylase (cadA) genes in Escherichia coli

  2017cited by this paper
• Engineering a new metabolic pathway for itaconate production in Pichia stipitis from xylose

  2017cited by this paper
• Identification of an itaconic acid degrading pathway in itaconic acid producing Aspergillus terreus

  2016cited by this paper
• Itaconic acid – a versatile building block for renewable polyesters with enhanced functionality

  2016cited by this paper
• Enhancing Cellulase Production in Thermophilic Fungus Myceliophthora thermophila ATCC42464 by RNA Interference of cre1 Gene Expression.

  2015cited by this paper
• Overexpression of the phosphofructokinase encoding gene is crucial for achieving high production of D-lactate in Corynebacterium glutamicum under oxygen deprivation

  2015cited by this paper
• Genomic insights into the fungal lignocellulolytic system of Myceliophthora thermophila

  2014cited by this paper
• Improving itaconic acid production through genetic engineering of an industrial Aspergillus terreus strain

  2014influential reference
• A systems biology approach for the identification of target genes for the improvement of itaconic acid production in Aspergillus species

  2013cited by this paper
• Manipulating redox and ATP balancing for improved production of succinate in E. coli.

  2011cited by this paper
• Comparative genomic analysis of the thermophilic biomass-degrading fungi Myceliophthora thermophila and Thielavia terrestris

  2011influential reference
• A clone-based transcriptomics approach for the identification of genes relevant for itaconic acid production in Aspergillus.

  2011cited by this paper
• Enhancing itaconic acid production by Aspergillus terreus

  2010cited by this paper
• Compositional Analysis of Lignocellulosic Feedstocks. 1. Review and Description of Methods

  2010cited by this paper
• Green energy strategies for sustainable development

  2006cited by this paper
• The subcellular organization of itaconate biosynthesis in Aspergillus terreus

  1991cited by this paper
• Biosynthesis of itaconic acid in Aspergillus terreus. I. Tracer studies with C14-labeled substrates.

  1957cited by this paper

• No citing papers are available for this paper.