Bio-based Isopropanol via Fermentation: A Renewable Route to a Key Solvent and Fuel Additive

Introduction

Isopropanol (IPA), also known as isopropyl alcohol, is a widely used solvent and chemical intermediate in pharmaceuticals, personal care, disinfectants, and coatings. It’s also being explored as a fuel additive and potential drop-in biofuel. Traditionally, IPA is derived from propene (a petroleum derivative) via hydration, contributing to fossil resource depletion and carbon emissions.

Bio-based isopropanol offers a sustainable, renewable alternative. Through microbial fermentation, sugars and biomass feedstocks can be converted into IPA using engineered microbes, mimicking or improving upon natural metabolic pathways. This bioprocess eliminates dependence on fossil hydrocarbons and reduces the carbon footprint of isopropanol production.

What Products Are Produced?

• Isopropanol (IPA) – Renewable, bio-based
• Applications:
• Solvent in pharmaceuticals, paints, cosmetics
• Antiseptic/disinfectant
• Fuel additive / biofuel candidate
• Intermediate for acetone, isopropyl esters

Pathways and Production Methods

1. Fermentative Route via Acetone-Butanol-Ethanol (ABE) Pathway

• Substrate: Glucose or lignocellulosic sugars
• Clostridium species naturally produce acetone
• Engineered strains (e.g., Clostridium beijerinckii, E. coli) express secondary alcohol dehydrogenase (SADH) to convert acetone → IPA

2. Direct IPA Pathway Engineering

• Glucose → pyruvate → acetolactate → acetoin → isopropanol
• Introduced synthetic pathway in E. coli using genes from Clostridium, Klebsiella, etc.

3. Gas Fermentation

• CO/CO₂ + H₂ → Acetyl-CoA → IPA
• Advanced route under development using acetogenic bacteria

Catalysts and Key Tools Used

Microbial Hosts:

• Clostridium acetobutylicum, Clostridium ljungdahlii
• E. coli (engineered with isopropanol pathway)
• Cupriavidus necator for syngas utilization

Key Enzymes:

• Secondary alcohol dehydrogenase (SADH)
• Acetone carboxylase (for acetone recycling)
• Acetolactate synthase, acetoin reductase

Tools:

• CRISPR-Cas pathway editing
• Redox balancing for cofactor (NADH/NADPH) needs
• Fermentation optimization (pH, gas sparging)
• Adaptive laboratory evolution for tolerance

Case Study: Green Biologics (UK/USA)

Highlights

• Developed Clostridium strains for IPA and n-butanol production
• Used ABE fermentation modification to boost IPA yield
• Produced commercial-grade bio-isopropanol for use in hand sanitizers and coatings

Timeline

• 2013 – Engineered pathway for isopropanol via acetone reduction
• 2016 – US bio-refinery launched in Minnesota
• 2019 – Market launch of bio-based IPA under the BioPure™ brand
• 2022 – Acquired by Locus Fermentation Solutions

Global and Indian Startups Working in This Area

Global

• Green Biologics (UK/USA) – Fermentation-derived IPA and butanol
• LanzaTech (USA) – Gas fermentation to isopropanol
• Gevo (USA) – Mixed alcohol fuels including IPA
• Cargill (USA) – Exploring sugar-to-alcohol fermentation

India

• Godavari Biorefineries – Fermentation of sugar-based alcohols
• IIT Delhi & NCL Pune – Research on metabolic engineering of IPA pathways
• Praj Industries – Piloting second-gen fermentation for C3–C4 alcohols
• DBT-ICGEB – Working on Clostridium-based platform strains for IPA

Market and Demand

The global isopropanol market was valued at USD 4.2 billion in 2023, projected to reach USD 5.8 billion by 2030 at a CAGR of ~5%. Bio-based IPA is growing faster, with a CAGR of 10–12%, driven by sustainability demands.

Major Use Segments:

• Pharmaceuticals and disinfectants (especially post-COVID)
• Solvents in paints, inks, and cosmetics
• Fuel additives and bio-blending components
• Renewable intermediates for acetone, esters

Key Growth Drivers

• Need for fossil-free solvents in pharma and personal care
• Rapid expansion of bio-disinfectants and hand sanitizers
• Potential use as a biofuel additive with low vapor pressure
• National policies promoting bio-C3 and C4 alcohols
• Feasibility of retrofitting ethanol plants for IPA fermentation

Challenges to Address

• Toxicity of intermediates (acetone, acetoin) to microbes
• Volatility and separation costs in downstream processing
• Strain stability and high-titer productivity
• In India: Lack of dedicated policy incentives for C3 bio-alcohols

Progress Indicators

• 2012–2014 – SADH gene integration in Clostridium for IPA
• 2016 – Green Biologics begins commercial production
• 2020 – COVID drives bio-IPA demand in sanitizers
• 2023 – Fermentation yields of >40 g/L achieved in engineered strains
• 2024 – Indian labs report pilot studies from molasses-based IPA

Technology Readiness Level (TRL)

• Glucose-based IPA fermentation: TRL 7–8 (demonstrated and commercialized)
• Gas fermentation to IPA: TRL 5–6
• In India: TRL 4–6, with active R&D in public-private labs

Conclusion

Bio-based isopropanol via fermentation is a scalable, sustainable alternative to petroleum-derived IPA, with vast potential in healthcare, solvents, and clean fuels. As synthetic biology improves titers, yields, and feedstock versatility, IPA joins the family of next-generation bio-alcohols with real commercial traction.

India, with its sugarcane-based ethanol ecosystem, can rapidly adapt fermentation infrastructure to include IPA production, provided strategic investments and policy support align with the growing demand for green solvents.

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