Genetically Modified Yeast for Lactic Acid Production

Introduction

Lactic acid is a versatile organic acid used in bioplastics (PLA), cosmetics, pharmaceuticals, and food preservatives. Traditionally produced using lactic acid bacteria (LAB) under controlled pH and nutrient-rich conditions, the process is often plagued by contamination, low yields, and substrate limitations.

To overcome these drawbacks, researchers have turned to genetically modified yeast (GMY)—particularly strains like Saccharomyces cerevisiae and Yarrowia lipolytica—to produce lactic acid with higher tolerance to stress, broader substrate use, and easier downstream processing. These engineered yeasts express heterologous lactate dehydrogenase (LDH) enzymes and undergo metabolic rewiring to divert carbon flux from ethanol to lactic acid. This approach offers a robust, scalable, and low-pH-compatible system for industrial lactic acid production, especially from renewable and lignocellulosic feedstocks.

What Products Are Produced?

• Lactic Acid (L-LA, D-LA, or racemic mixtures) – Feedstock for:
• PLA (Polylactic acid) – Bioplastics
• Lactate esters – Green solvents
• Food-grade acidulants and preservatives
• Cosmetic and pharmaceutical formulations

Pathways and Production Methods

1. Heterologous LDH Expression

• Introduction of bacterial or fungal LDH genes into yeast (e.g., ldhA, ldhL)
• Conversion of pyruvate → lactate, bypassing ethanol pathway

2. Ethanol Pathway Suppression

• Deletion or repression of PDC1, ADH1 genes in S. cerevisiae
• Redirects carbon flux from ethanol to lactic acid
• Increases NADH availability for LDH activity

3. pH-Tolerant and Osmotolerant Engineering

• Yeast strains selected or modified for low-pH tolerance
• Fermentation without the need for costly neutralizers like CaCO₃

4. Use of Diverse Substrates

• Utilization of glucose, xylose, glycerol, food waste, or lignocellulosic hydrolysates
• Consolidated bioprocessing with enzyme secretion (in some designs)

Catalysts and Key Tools Used

Engineered Microbes:

• Saccharomyces cerevisiae – CRISPR-modified for lactic acid yield
• Yarrowia lipolytica – Suited for fatty substrates and high titers
• Kluyveromyces marxianus – Thermotolerant and fast-growing
• Candida utilis – Used for mixed acid fermentation

Key Enzymes:

• LDH (L-lactate dehydrogenase) – Converts pyruvate to lactate
• Glucose transporters – Enhanced for higher uptake
• Redox balancers – To maintain NADH/NAD⁺ equilibrium

Fermentation Systems:

• Fed-batch or continuous stirred tank reactors
• Low-pH operation for cost-effective downstream purification
• Immobilized or cell-recycle systems for increased yield

Case Study: Jungbunzlauer (Austria/France) – PLA-Grade Lactic Acid from Yeast

Highlights

• Developed non-GMO and GMO yeast platforms for lactic acid
• Achieved >120 g/L lactic acid in fed-batch fermentation with modified yeast
• Supplied PLA-grade lactic acid to NatureWorks and Total Corbion PLA
• Focused on low-salt, low-waste processes for sustainable production

Timeline

• 2009 – Initiated yeast-based lactic acid R&D
• 2014 – Pilot-scale GM yeast strains evaluated
• 2018 – PLA-grade commercial production begins
• 2023 – Yeast fermentation plant upgraded with circular waste loops

Global and Indian Startups Working in This Area

Global

• NatureWorks (USA/Thailand) – PLA from lactic acid (GMO-based platform suppliers)
• Cargill + DSM (Netherlands/USA) – Joint venture for lactic acid from engineered yeast
• Galactic (Belgium) – Advanced yeast and bacteria fermentation for food-grade LA
• BASF and Corbion – Exploring yeast-based green solvent esters from lactic acid

India

• Praj Industries (Pune) – R&D on lignocellulosic to lactic acid via engineered yeasts
• IIT Madras, ICT Mumbai – Pilot work on GMO yeast for lactate from agro-waste
• CSIR-CFTRI and CSIR-IITR – Exploring lactic acid for food and pharma via synthetic biology
• Early-stage BIRAC startups – Investigating yeast-based bioplastic precursors

Market and Demand

The global lactic acid market was valued at USD 4.2 billion in 2023 and is projected to reach USD 7.5 billion by 2030, growing at a CAGR of ~8.5%. Key drivers include demand for PLA bioplastics, natural preservatives, and green solvents.

Major End-Use Segments:

• Bioplastics (PLA) – Packaging, textiles, automotive
• Food and beverages – Preservatives, pH regulators
• Pharmaceuticals – Drug carriers, calcium lactate
• Personal care and cosmetics – pH adjusters, exfoliants
• Green chemicals – Lactate esters, solvents, antifreeze

Key Growth Drivers

• Surging demand for biodegradable plastics (especially PLA)
• Need for non-pathogenic, pH-tolerant, scalable producers
• Ability to use low-cost agro-waste and glycerol
• Regulatory push for non-GMO LAB alternatives in food and pharma
• Alignment with low-carbon and low-salt fermentation processes

Challenges to Address

• Redox imbalance during high-titer lactate production
• Residual ethanol or glycerol by-products in engineered strains
• Strain stability and robustness under industrial conditions
• Toxicity from lignocellulosic inhibitors in second-gen feedstocks
• Regulatory barriers in food/pharma use of GMOs

Progress Indicators

• 2010 – Engineered yeast strains demonstrate lactate yields in lab
• 2015 – CRISPR tools used to fine-tune redox and carbon flux
• 2019 – First commercial yeast-based LA plant opens in EU
• 2022 – Indian research institutes achieve >80 g/L LA in bioreactor scale
• 2024 – Indian bioplastics startups explore PLA from yeast-derived LA

Genetically engineered yeast for lactic acid is at TRL 8–9 globally (fully commercialized), and TRL 5–6 in India, where academic and industrial pilot trials are ongoing.

Conclusion

Genetically modified yeast offers a next-generation platform for robust, scalable, and cost-effective lactic acid production. With the ability to thrive in low-pH conditions, consume diverse substrates, and integrate with downstream PLA or lactate ester production, GM yeast provides a clean, industrially viable route for this key green chemical.

As India ramps up its bioplastics, food-tech, and fermentation infrastructure, GM yeast for lactic acid stands as a critical enabler of sustainable manufacturing, bridging waste valorization and bio-based industry development.

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