Fermentation-Derived Isosorbide Production

Introduction

Isosorbide is a renewable, rigid, and thermally stable bicyclic diol derived from glucose. It plays a key role in the production of bioplastics (like polyethylene isosorbide terephthalate, PEIT), coatings, resins, and pharmaceuticals. Its fossil-based alternatives (like bisphenol A) are increasingly being phased out due to toxicity and endocrine-disrupting properties, positioning isosorbide as a safe and sustainable replacement.

Traditionally, isosorbide is produced from sorbitol, which itself is derived chemically from glucose. However, new fermentation-derived processes enable direct microbial production of isosorbide or bioconversion of glucose to sorbitol and then to isosorbide using engineered enzymatic systems—offering a cleaner, integrated pathway using renewable feedstocks and minimal chemical steps.

What Products Are Produced?

Isosorbide – Diol for:

• PEIT plastics (bio-alternative to PET)
• Polycarbonates, epoxy resins, and polyurethanes
• Coating resins and adhesives
• Pharmaceuticals and drug carriers

Pathways and Production Methods

1. Two-Step Fermentation–Catalysis Route

• Glucose → Sorbitol → Isosorbide
  • Step 1: Fermentative production of sorbitol using Zymomonas mobilis or E. coli
  • Step 2: Dehydration of sorbitol to isosorbide via acid or solid catalysts

2. One-Pot Biocatalytic Conversion

• Direct enzymatic cascade: Glucose → Sorbitol → 1,4-Sorbitan → Isosorbide
• Enzyme cocktail includes:
  • Glucose reductase, sorbitol dehydratase, dehydratase isomerase

3. Engineered Microbial Pathways

• Synthetic biology approach in E. coli or Corynebacterium glutamicum:
  • Integrate sorbitol biosynthesis, dehydration enzymes, and isomerization modules
  • Whole-cell catalysis under mild conditions, eliminating external acid use

Catalysts and Key Tools Used

Enzymes:

• Sorbitol dehydrogenase
• Sorbitol dehydratase
• Isosorbide isomerase (engineered)
• Aldose reductase for glucose to sorbitol

Engineering Tools:

• Modular metabolic pathway assembly
• CRISPR/Cas9 for gene integration
• Dynamic promoter systems to balance toxic intermediates
• Solid acid catalysts (e.g., Amberlyst)

Host Microbes:

• E. coli, Z. mobilis, C. glutamicum, and yeasts with osmotic tolerance

Case Study: Roquette & University of Lille – Integrated Biobased Isosorbide

Highlights

• Developed integrated process for glucose → sorbitol → isosorbide
• Used enzymatic bioreduction + continuous-flow catalytic dehydration
• Achieved high purity (>98%) suitable for food contact polymers
• Roquette commercialized the product as POLYSORB® Isosorbide

Timeline

• 2010 – Lab-scale integrated sorbitol-to-isosorbide route
• 2015 – Demonstration plant in France
• 2019 – Isosorbide used in PEIT bio-bottle prototypes
• 2023 – Roquette launches isosorbide-based polyesters for packaging

Global and Indian Startups Working in This Area

Global

• Roquette (France) – Leading commercial supplier (POLYSORB®)

• Mitsubishi Chemical (Japan) – Isosorbide-based polycarbonates
• Metabolic Explorer (France) – Developing direct fermentation routes
• TTC (Thailand) – Isosorbide from starch-based sorbitol

India

• CSIR-IICT Hyderabad – Biocatalytic conversion of glucose to sorbitol and isosorbide
• IIT Guwahati – Enzyme discovery for isosorbide dehydration
• Godavari Biorefineries – Exploring sugarcane-based sorbitol-to-isosorbide routes
• Startups under BIRAC – Working on isosorbide-based bioplastics and drug carriers

Market and Demand

The global isosorbide market was valued at USD 540 million in 2023, expected to reach USD 1.1 billion by 2030, at a CAGR of ~10%.

Major End-Use Segments:

• Bioplastics (PEIT, polycarbonates) – Bottles, films, durable goods
• Epoxy resins and coatings – Industrial and automotive use
• Pharmaceuticals – Drug carriers and excipients
• Cosmetics and personal care – Biocompatible solvents

Key Growth Drivers

• Need for BPA-free polymers in food packaging
• Push for biodegradable and bio-content certified plastics
• Growing sorbitol capacity from sugarcane and corn feedstocks
• Low toxicity and high thermal stability of isosorbide
• Regulatory interest in replacing fossil diols with renewable options

Challenges to Address

• Energy-intensive dehydration step if chemical route is used
• Product recovery from aqueous broth with high boiling point
• Lack of cost-competitive routes for direct microbial production
• In India: market linkages for bioplastics using isosorbide are limited
• Enzyme stability and specificity remain key barriers for full biosynthesis

Progress Indicators

• 2008–2012 – Isosorbide explored as PET substitute monomer
• 2015 – Commercial plants for isosorbide from sorbitol commissioned in EU
• 2018 – Enzyme engineering breakthroughs for biocatalytic dehydration
• 2022 – Indian academic labs enter enzymatic process development
• 2024 – Biobased PEIT films tested in packaging trials in India

Globally, isosorbide via fermentation–catalysis hybrid route is at TRL 8–9; direct microbial biosynthesis is at TRL 5–6. In India, TRL 4–6, with enzymatic modules and fermentation under development.

Conclusion

Fermentation-derived isosorbide is a cornerstone of the next-generation bioplastics and sustainable materials industry. With applications in food packaging, automotive coatings, and BPA-free polymers, isosorbide offers a renewable and safer alternative to fossil-based diols.

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