Fatty Acid Synthase for Hydrocarbons

Introduction

Fatty Acid Synthase (FAS) is a multi-enzyme complex that plays a central role in the biosynthesis of long-chain fatty acids from simple building blocks like acetyl-CoA and malonyl-CoA. Fatty acids are not only essential components of cell membranes but also serve as feedstocks for the production of hydrocarbons, including biodiesel, alkanes, alkenes, and waxes.

In metabolic engineering, harnessing and optimizing the FAS system allows for the bio-based production of hydrocarbon fuels and specialty oleochemicals. These biologically derived hydrocarbons can replace or supplement fossil fuels in sectors such as transportation, aviation, and chemical manufacturing, advancing the vision of a renewable carbon economy.

What Products Are Produced?

Through engineered fatty acid synthesis and downstream processing, the following products can be obtained:

• Straight-chain alkanes and alkenes (gasoline, diesel-range hydrocarbons)
• Fatty alcohols (used in detergents, cosmetics)
• Fatty acid methyl esters (FAMEs) – biodiesel components
• Wax esters and lubricants
• Specialty chemicals – α-olefins, dicarboxylic acids

Pathways and Production Methods

1. Native FAS Pathway Enhancement
• Overexpression of FAS subunits (FAS I/II) in microbes like E. coli, S. cerevisiae, and cyanobacteria.
• Increases intracellular fatty acid pools for hydrocarbon conversion.
2. Decarboxylation to Alkane
• Fatty acids → fatty aldehydes → alkanes using enzymes like aldehyde-deformylating oxygenase (ADO).
3. Esterification & Transesterification
• FAS products are converted into FAMEs using lipases or chemical catalysts.
4. Chain Length Modulation
• Engineering thioesterases or elongases to produce C8–C20 chain lengths for fuel applications.
5. Photosynthetic Hydrocarbon Production
• FAS pathway integrated with CO₂ fixation in cyanobacteria or algae to convert solar energy into drop-in fuels.

Catalysts and Key Tools Used

• Enzymes:

• Fatty acid synthase (FAS I in fungi/mammals, FAS II in bacteria/plants)
• Thioesterases (chain length-specific)
• Aldehyde deformylating oxygenase (ADO), fatty acid reductases (FAR)
• Lipases and esterases for biodiesel conversion

• Engineering Tools:

• CRISPR-Cas for pathway optimization
• Flux balance models to tune carbon allocation
• Synthetic promoters and operons to control gene expression
• Adaptive laboratory evolution (ALE) for tolerance

• Feedstocks:

• Sugars, glycerol, CO₂ (in autotrophs), waste oils

Case Study: LS9 Inc. – From Sugar to Diesel

Highlights

• Engineered E. coli with modified FAS and hydrocarbon pathways to directly produce alkanes and esters.
• Fermented sugar into renewable diesel and fatty alcohols using a single fermentation step.
• Employed microbial consortia and synthetic biology for high yield and scalability.
• Acquired by Renewable Energy Group in 2013 to commercialize renewable diesel.

Timeline

• 2007 – Founded in California with focus on microbial fuel production
• 2009 – Pilot plant operational; microbial diesel meets ASTM D975 fuel specs
• 2011 – Scaled production to 75,000-liter fermenters
• 2013 – Acquired by REG for large-scale renewable diesel production
• 2020–2023 – Legacy technologies integrated into advanced hydrocarbon platforms

Global and Indian Startups Working in This Area

Global

• LS9 (USA) – Engineered FAS for microbial hydrocarbon fuels
• Amyris (USA) – Terpenoid and FAS-based renewable jet fuels and lubricants
• Synthetic Genomics (USA) – Algal hydrocarbons via photosynthetic FAS
• Neste (Finland) – Uses microbial oils as part of its bio-based diesel streams

India

• Praj Industries (Pune) – Developing microbial lipid platforms from sugarcane residues
• Sea6 Energy (Bengaluru) – Using marine biomass and engineered algae for bio-oil production
• IIT Guwahati & DBT-ICGEB – Focused on cyanobacterial FAS pathway engineering
• CSIR-IIP Dehradun – Collaborating on algal and microbial fatty acid-derived fuels

Market and Demand

The global fatty acid-based hydrocarbon market is projected to grow from USD 2.9 billion in 2023 to USD 6.7 billion by 2030, with a CAGR of ~12%, driven by biofuel mandates and demand for renewable chemicals.

Major End-Use Segments:

• Sustainable Aviation Fuel (SAF) – via hydrotreated esters and fatty acids (HEFA)
• Diesel and Marine Fuels – Drop-in ready, low-sulfur fuels
• Personal Care & Oleochemicals – Fatty alcohols and acids
• Industrial Lubricants & Waxes – Biobased and biodegradabl

Key Growth Drivers

• High carbon efficiency and yield of FAS-based pathways
• Drop-in compatibility with current fuel infrastructure
• CO₂ fixation potential in algae and photosynthetic microbes
• Availability of waste biomass and oils as substrates
• Regulatory push for low-carbon fuel standards globally

Challenges to Address

• Product toxicity: Fatty acids and alkanes can inhibit microbial growth
• NADPH demand: Fatty acid biosynthesis is energy-intensive
• Byproduct accumulation: Glycerol, acetate, or unwanted lipids reduce yield
• Scale-up constraints: Viscosity and foam issues in lipid-rich cultures
• Strain robustness: Engineered microbes often sensitive to fermentation stress

Progress Indicators

• 2009 – First microbial diesel meeting fuel standards produced
• 2014 – CRISPR-enabled modulation of FAS in E. coli and yeast
• 2018 – Cyanobacterial FAS pathways optimized for direct alkane production
• 2021 – Indian studies demonstrate fatty acid production from sugarcane bagasse
• 2023 – Photosynthetic FAS integration in algae reaches TRL 6–7

Fatty acid-based hydrocarbon production is at TRL 7–9 for biodiesel and alcohols in model microbes; advanced alkane production via synthetic pathways in autotrophs is at TRL 5–6.

Conclusion

Fatty acid synthase is a versatile and powerful biosynthetic engine for producing renewable hydrocarbons. From microbial diesel to jet fuel precursors, FAS-driven platforms are helping build a low-carbon, bio-based fuel economy.

With India’s strengths in agro-feedstocks, fermentation infrastructure, and biotech R&D, scaling FAS-based hydrocarbon technologies can serve both energy security and climate goals—making biofuels not just green, but viable.

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