Bio-based Production of Azelaic Acid

Introduction

Azelaic acid (nonanedioic acid) is a naturally occurring C9 dicarboxylic acid valued for its applications in personal care (acne treatments, skin lightening), polymer manufacturing, lubricants, and plasticizers. Traditionally produced by ozonolysis of oleic acid, the conventional method is energy-intensive and environmentally hazardous due to ozone use and generation of toxic byproducts.

With the growing shift toward sustainable chemicals, bio-based production of azelaic acid has emerged as an alternative. This involves the microbial oxidation of unsaturated fatty acids (mainly oleic acid or ricinoleic acid) using enzymes like lipoxygenases, monooxygenases, or engineered whole-cell biocatalysts. It enables green, selective oxidation without the use of ozone or nitric acid, offering improved environmental and safety profiles.

What Products Are Produced?

• Azelaic Acid (C9H16O4)
• Applications:
• Cosmetics and dermatology – acne creams, hyperpigmentation treatment
• Polyesters and nylons – flexible, biodegradable polymers
• Lubricants – base oils for biodegradable lubricants
• Plasticizers – eco-friendly alternatives to phthalates
• Coatings – alkyd and powder coatings

Pathways and Production Methods

1. Chemical Route (Conventional)

• Ozonolysis of oleic acid → azelaic acid + pelargonic acid
• Drawbacks: High energy, ozone hazards, non-selective byproducts

2. Bio-based Oxidation of Oleic Acid

• Oleic acid (C18:1) → azelaic acid + pelargonic acid
• Enzymes Involved:
• Lipoxygenases – catalyze hydroperoxidation of double bonds
• Baeyer–Villiger monooxygenases (BVMOs) – oxidize mid-chain epoxides
• Peroxidases or P450s – terminal oxidation for chain cleavage

3. Microbial Bioconversion

Whole-cell oxidation using:

• Candida tropicalis, Yarrowia lipolytica, or engineered E. coli
• Converts oleic acid via ω-oxidation and β-oxidation pathways to yield azelaic acid

Substrate: Oleic acid or castor oil derivatives

Catalysts and Key Tools Used

Enzymes:

• Lipoxygenases – regioselective oxidation
• Alcohol and aldehyde dehydrogenases – facilitate ω-oxidation
• Baeyer–Villiger monooxygenases (BVMOs) – for selective cleavage of intermediates

Microbial Hosts:

• Yarrowia lipolytica – naturally oleaginous yeast, rich in oxidation machinery
• E. coli – engineered to express ω-oxidation enzymes
• Candida tropicalis – capable of terminal oxidation of fatty acids

Tools:

• Fed-batch fermentation with oleic acid feeding
• Immobilized enzymes for continuous oxidation
• Genetic engineering for increased terminal oxidation and epoxide processing

Case Study: Novozymes – Biocatalytic Azelaic Acid for Personal Care

Highlights

• Enzymatic oxidation platform using immobilized oxidoreductases
• Converts oleic acid from non-GMO sunflower oil to azelaic acid
• Developed in collaboration with personal care brands for “clean label” formulation

Timeline

• 2014 – Pilot trials with lipoxygenase-based conversion
• 2017 – Launched bio-based azelaic acid for skin care
• 2021 – Expanded process to oleochemical-grade purity for coatings
• 2024 – Entered partnership with BASF for large-scale bio-oxidation system

Global and Indian Startups Working in This Area

Global

• Matrica (Italy) – JV of Versalis and Novamont; makes azelaic acid from vegetable oils
• Croda (UK) – Uses enzymatic oxidation to produce high-purity azelaic acid
• Metabolic Explorer (France) – Working on engineered microbes for long-chain dicarboxylic acids
• Evonik – Advanced ω-oxidation pathways in Yarrowia

India

• Godavari Biorefineries – Exploring castor oil to azelaic acid via green oxidation
• IIT Guwahati – Research on peroxidase enzymes for mid-chain oxidation
• Biovantage Agritech – Pilot plant studies for azelaic acid from industrial oleic acid
• Praan Biosciences – Developing enzymatic platforms for oleochemical conversions

Market and Demand

The global azelaic acid market is valued at USD 300 million (2023) and expected to reach USD 520 million by 2030, with a CAGR of 7.6%.

Major Use Segments:

• Cosmetics & dermatology – skin creams, acne treatment (over 35% market share)
• Polymer intermediates – nylons, polyesters, resins
• Industrial lubricants – biodegradable esters
• Plasticizers and coatings

Key Growth Drivers

• Rising demand for sustainable personal care ingredients
• Regulatory pressure to phase out ozonolysis-based oxidation processes
• Growth of green chemistry in polymer manufacturing
• Increased availability of renewable feedstocks like non-edible oils

Challenges to Address

• Substrate inhibition by fatty acids at high concentrations
• Enzyme systems require cofactor regeneration and oxygenation control
• Purification of azelaic acid from complex fermentation broth
• In India: Limited scale-up expertise in enzyme-based oleochemical oxidation

Progress Indicators

• 2010 – Academic studies on bio-oxidation of oleic acid begin
• 2015 – Lipase/lipoxygenase combinations show promise
• 2018 – Biocatalyst immobilization improves conversion efficiency
• 2023 – Commercial-scale fermentation of azelaic acid from castor oil derivatives

Enzymatic azelaic acid production: TRL 7–8 globally (market-ready). In India: TRL 4–5, moving toward pilot-scale demonstration

Conclusion

The bio-based production of azelaic acid offers a clean, renewable, and scalable route to an important dicarboxylic acid used in cosmetics, polymers, lubricants, and green solvents. By replacing ozone with selective enzyme systems, companies can achieve high product purity with minimal environmental impact.

As the global market demands biobased solutions, India can leverage its abundant castor oil, growing biotech infrastructure, and oleochemical industry to emerge as a regional leader in green azelaic acid production—especially if investments continue in enzyme development, bioreactor design, and application-linked partnerships.

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