Microbial Production of Muconic Acid

Introduction

Muconic acid is an unsaturated dicarboxylic acid with immense industrial value. It serves as a precursor for adipic acid, terephthalic acid, caprolactam, and nylon derivatives, making it a vital platform chemical for bioplastics, synthetic fibers, coatings, and resins. Conventionally, these polymers are produced from petroleum-based aromatics, leading to high greenhouse gas emissions and resource depletion.

Through microbial biosynthesis, muconic acid can be produced from renewable feedstocks like glucose, lignin, and glycerol. Using synthetic biology and metabolic engineering, researchers are now reprogramming microbes such as E. coli, Saccharomyces cerevisiae, and Pseudomonas putida to convert biomass-derived carbon sources into cis,cis-muconic acid (ccMA)—enabling a sustainable route to major chemical building blocks

What Products Are Produced?

• cis,cis-Muconic Acid (ccMA) – A renewable intermediate for:
• Adipic acid → Nylon-6,6
• Terephthalic acid → PET plastics
• Caprolactam → Nylon-6
• Other dicarboxylic acid derivatives

Pathways and Production Methods

1. Shikimate Pathway Engineering (from Sugars)

• Glucose → PEP + E4P → 3-dehydroshikimate → protocatechuic acid (PCA) → catechol → muconic acid
• Engineered in E. coli and yeast by overexpressing dehydratase, decarboxylase, and dioxygenase enzymes

2. Lignin Valorization Route

• Lignin-derived aromatic compounds → catechol / PCA / vanillate → muconic acid
• Pseudomonas putida used to funnel aromatic breakdown into the beta-ketoadipate pathway

3. Glycerol and Mixed Feedstock Conversion

• Alternative carbon sources like glycerol and glycerol-glucose mixes are converted to muconate in engineered strains with optimized redox balance

Catalysts and Key Tools Used

Microbial Platforms:

• Escherichia coli – Fast-growing, well-characterized
• Saccharomyces cerevisiae – Robust industrial host
• Pseudomonas putida – Aromatic tolerance and lignin metabolizer

Key Enzymes:

• 3-dehydroshikimate dehydratase (AroZ)
• Protocatechuate decarboxylase (AroY)
• Catechol 1,2-dioxygenase (CatA)

Tools and Strategies:

• CRISPR-Cas9 and modular metabolic pathway assembly
• Promoter tuning and dynamic regulation
• Transporter engineering to improve muconic acid export
• Flux balance optimization using modeling tools (COBRA, OptKnock)

Case Study: Amyris and University of Minnesota Collaboration

Highlights

• Engineered S. cerevisiae with bacterial genes to convert glucose to ccMA
• Achieved >2 g/L muconic acid in fed-batch fermentation
• Demonstrated conversion of muconate to nylon monomers and bioplastics

Timeline

• 2013 – UMN develops first yeast strains for ccMA
• 2016 – Amyris joins to scale and commercialize bio-nylon
• 2019 – Fed-batch process optimized for >90% theoretical yield
• 2022 – Pilot plant trials in Brazil with sugarcane-derived feedstock

Global and Indian Startups Working in This Area

Global

• Amyris (USA) – ccMA for bioplastics and nylon
• Zymergen (USA) – High-throughput strain engineering for muconate
• NexantECA (UK) – Tech scouting for biobased aromatics
• BioAmber (Canada) – Downstream valorization to adipic acid

India

• IIT Delhi & NCL Pune – Shikimate pathway rewiring in E. coli
• IISER Bhopal – Lignin valorization to muconate using Pseudomonas
• ICT Mumbai – Sugar-to-aromatic platform strains under BIRAC funding
• Bioscale India – Lab-scale synthesis of adipic acid from muconate

Market and Demand

The muconic acid market is currently nascent, valued around USD 15–20 million, but expected to grow rapidly with the adoption of biobased nylons and PET. By 2030, it could surpass USD 150 million, with a CAGR of ~25%, driven by downstream monomers.

Key Use Segments:

• Nylon-6,6 and Nylon-6
• PET bottles and bioplastics
• Polyurethanes and adhesives
• Green solvents and coatings

Key Growth Drivers

• Replacement of fossil-derived adipic and terephthalic acids
• Global push for carbon-neutral polymers
• Advancements in metabolic pathway optimization
• Demand from packaging, automotive, and textile sectors
• Integration with lignin valorization and circular economy goals

Challenges to Address

• Toxicity of intermediates (e.g., catechol) to host cells
• Strain stability and production yield under industrial conditions
• Efficient downstream recovery of muconic acid
• In India: Need for scale-up infrastructure and biorefinery integration

Progress Indicators

• 2013 – Microbial muconate production first reported
• 2016–2018 – Fed-batch optimization and pilot strain development
• 2020 – Industrial interest from bio-nylon and packaging sectors
• 2023 – Indian research institutes report 5+ g/L yields from glucose
• 2024 – Commercial talks for bio-nylon intermediates begin globally

Sugar-based muconic acid: TRL 6–7 (pilot stage). Lignin-based routes: TRL 4–5 (early pilot). In India: Active work at TRL 3–6, with several promising academic-to-startup transitions

Conclusion

Microbial production of muconic acid represents a highly promising route to sustainable polymers and aromatics, breaking away from fossil-based benzene and xylene derivatives. With continued progress in synthetic biology, lignin valorization, and fermentation scale-up, ccMA can unlock a new generation of green plastics and nylons.

India’s bioeconomy push and academic R&D pipeline can enable it to become a regional leader in biobased muconate, especially by leveraging sugar and lignin waste streams from agriculture.

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