In a world drowning in plastic waste, scientists are turning to tiny biological factories for solutions.
Imagine a world where the plastic in your water bottle, food packaging, and even the fibers in your clothing comes not from petroleum, but from the metabolic processes of microorganisms.
While lactic acid has traditionally been produced through fermentation by lactic acid bacteria, these organisms have limitations in industrial settings. Engineered yeast combines the hardiness of yeast with the ability to produce lactic acid efficiently, even at low pH levels that would inhibit other microbes 7 .
Saccharomyces cerevisiae might be famous for making bread rise and fermenting beer, but to scientists, it represents an ideal host for industrial biotechnology.
Yeast converts pyruvate into ethanol and CO₂ via pyruvate decarboxylase (PDC) enzymes
Redirect metabolic flow from ethanol to lactic acid production
Yeast is remarkably tolerant of acidic conditions—exactly the environment created by lactic acid accumulation 7
Foundational work by Adachi and colleagues demonstrated the feasibility of engineering yeast for lactic acid production at low pH.
| Strain Characteristics | Sugar Source | Lactic Acid Yield (g/g sugar) |
|---|---|---|
| PDC-intact + LDH | Glucose | ~0.18-0.22 |
| PDC-deficient + LDH | Glucose | ~0.67-0.80 |
| PDC-intact + LDH | Xylose | ~0.69 |
| PDC-deficient + LDH | Xylose | ~0.80 |
| Aeration Condition | Lactic Acid Productivity | Cell Growth |
|---|---|---|
| Anaerobic | Low | Severely impaired |
| Microaerophilic | Moderate | Improved |
| Aerobic | High (on glucose) | Good |
When grown on xylose, even strains with intact PDC genes preferentially produce lactic acid over ethanol 9 . This substrate-dependent regulation opens alternative engineering strategies.
Microaerophilic fermentation with limited oxygen availability (around 2% dissolved oxygen) maintains lactic acid production while supporting better cell growth than anaerobic conditions 7 .
| Characteristic | Lactic Acid Bacteria | Engineered Yeast |
|---|---|---|
| Acid Tolerance | Moderate | High |
| Substrate Range | Limited | Broad (including xylose) |
| Genetic Tools | Limited | Extensive |
| Process Robustness | Requires neutralization | Can ferment at low pH |
| Byproduct Formation | Minimal | Can be engineered for purity |
CRISPR-Cas9 and other systems enable precise deletion of PDC genes, redirecting metabolic flux from ethanol to lactic acid production 7 .
Strong, constitutive promoters ensure high-level expression of introduced LDH genes, maximizing conversion of pyruvate to lactate 9 .
DNA constructs that allow stable integration of foreign genes into specific locations in the yeast chromosome 2 .
Aerobic and anaerobic fermentation systems that enable precise control of oxygen levels, crucial for optimizing lactic acid yields 7 .
Protocols for measuring LDH and PDC enzyme activities to verify successful engineering and understand metabolic flux distributions 7 .
The engineering of Saccharomyces cerevisiae for lactic acid production represents more than a technical achievement—it demonstrates how synthetic biology can rewire ancient biological processes to address modern environmental challenges.
The transformation of yeast from a maker of bread and beer to a producer of biodegradable plastics exemplifies the potential of biotechnology to create sustainable alternatives to petrochemical-based products. As research advances, the vision of a circular bioeconomy comes increasingly within reach, one engineered microbe at a time.
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