Harnessing engineered microorganisms for sustainable production of glycolic acid and ethylene glycol
Imagine a world where the chemicals in your skincare products, the antifreeze in your car, and the biodegradable packaging of your favorite foods are all produced by microscopic organisms feeding on renewable plant materials.
The smallest alpha-hydroxy acid with applications in cosmetics and biodegradable plastics
Essential for antifreeze and as a precursor for polyester fibers and PET plastics
Traditionally, both chemicals have been produced from petrochemical resources through processes that often require toxic intermediates like formaldehyde. But growing environmental concerns and the push for sustainability have driven scientists to explore cleaner alternatives. The answer lies in harnessing the power of engineered microorganisms as tiny chemical factories 1 8 .
At its core, metabolic engineering for chemical production involves three key steps: finding a suitable pathway, engineering the host organism, and optimizing production. For glycolic acid and ethylene glycol, the challenge was particularly interesting since no natural microbial pathways exist to directly produce these chemicals from cheap, renewable feedstocks 1 .
Scientists have designed several synthetic metabolic pathways in microorganisms such as Escherichia coli, Corynebacterium glutamicum, and yeasts including Saccharomyces cerevisiae and Kluyveromyces lactis. These engineered microbes can convert various sugar sources into the desired two-carbon chemicals 1 .
Breaks down D-xylose and can be combined with other pathways for efficient production 6
A natural metabolic route that can be engineered to produce glycolic acid 6
Produces glycolaldehyde as an intermediate for ethylene glycol production 1
While bacteria like E. coli were initially the preferred hosts for metabolic engineering, yeasts have emerged as powerful alternatives due to their natural tolerance to acidic conditions. This is particularly important for producing glycolic acid, which is most stable and easily recovered at low pH 8 .
In a landmark study, researchers engineered both Saccharomyces cerevisiae (baker's yeast) and Kluyveromyces lactis (a relative used in cheese making) to produce glycolic acid. They discovered that K. lactis was significantly more effective, producing up to 15 grams per liter of glycolic acid in bioreactor cultivations 8 .
15 g/L glycolic acid produced by engineered K. lactis
In 2018, a team of researchers published a comprehensive study demonstrating an efficient method for producing glycolic acid from D-xylose using engineered E. coli 6 . Their strategy involved creatively linking two metabolic pathways: the Dahms pathway (for D-xylose conversion) and the glyoxylate bypass (for glyoxylate production).
Disrupted the xylAB and glcD genes to prevent natural metabolism of D-xylose and glycolate 6
Introduced xylonate dehydratase gene (xdh) from Caulobacter crescentus to enable the Dahms pathway 6
Identified rate-limiting steps and balanced gene expression in both pathways for maximum efficiency 6
Created the GA19 strain with optimized pathway expression 6
The final engineered strain, designated GA19, achieved impressive results: 4.57 grams per liter of glycolic acid with a yield of 0.46 grams per gram of D-xylose 6 . While the absolute titer might seem modest compared to some industrial processes, this represented the highest value achieved for glycolic acid production in engineered E. coli through the Dahms pathway at the time of publication.
Glycolic Acid Titer
Yield from D-xylose
Engineered Strain
The research also highlighted D-xylose as a promising feedstock since it can be derived from agricultural waste products like corn cobs and straw, providing a renewable and inexpensive carbon source that doesn't compete with food production.
| Research Reagent | Function in Production | Examples/Specific Types |
|---|---|---|
| Engineered Microorganisms | Biocatalysts that convert feedstocks into desired products | E. coli 1 6 , C. glutamicum 1 , S. cerevisiae 1 8 , K. lactis 1 8 |
| Carbon Sources | Renewable feedstocks that microbes metabolize | D-xylose 1 6 , glucose 1 , ethanol 1 8 |
| Key Enzymes | Catalyze specific metabolic reactions in engineered pathways | Glyoxylate reductase (ycdW, GLYR1) 1 8 , isocitrate lyase (AceA) 1 6 , xylonate dehydratase (yagF) 6 |
| Bioreactors | Controlled environment for microbial cultivation and production | Sealed aerated stirred tank reactors (SSTR) with compressed oxygen supply 3 |
| Purification Materials | Separate and purify the final product from the fermentation broth | Weak basic anion-exchange resins 3 |
| Analytical Tools | Measure product concentration, yield, and purity | HPLC (High-Performance Liquid Chromatography) 8 |
Precise modifications to microbial genomes enable redirection of metabolic fluxes toward desired products.
Advanced bioreactors provide optimal conditions for microbial growth and chemical production at scale.
Performance of various engineered microorganisms in producing glycolic acid and ethylene glycol from different carbon sources 1 .
| Host Microorganism | Product | Carbon Source | Titer (g/L) | Yield (g/g) |
|---|---|---|---|---|
| E. coli Mgly434 | Glycolic Acid | Glucose | 65.5 | 0.77 |
| E. coli WL3110 | Ethylene Glycol | D-xylose | 108.2 | 0.36 |
| E. coli BL21(DE3) | Ethylene Glycol | D-xylose | 72.0 | 0.40 |
| K. lactis H3954 | Glycolic Acid | Ethanol | 15.0 | 0.52 |
| E. coli MG1655 | Glycolic Acid | D-xylose | 44.0 | 0.44 |
Highest Ethylene Glycol Titer
E. coli WL3110 on D-xyloseHighest Yield
E. coli Mgly434 on glucoseHighest Glycolic Acid Titer
E. coli Mgly434 on glucoseThe data reveal several interesting patterns. First, different microbial hosts show varying production capabilities, with some E. coli strains achieving remarkably high titers of both glycolic acid and ethylene glycol. Second, the carbon source significantly influences performance—engineered strains can utilize various feedstocks, providing flexibility based on local availability and cost. Third, there's typically a trade-off between titer and yield, with processes optimized for maximum production per volume (titer) sometimes sacrificing efficiency of carbon conversion (yield).
| Metabolic Pathway | Typical Host | Key Features | Typical Carbon Source |
|---|---|---|---|
| Glyoxylate Shunt | E. coli, Yeast | High yield from C2 compounds; naturally exists but requires engineering to redirect flux | Ethanol, Acetate |
| Dahms Pathway | E. coli | Direct conversion of pentose sugars; enables use of hemicellulose waste streams | D-xylose |
| D-xylulose-1-P Pathway | E. coli | High theoretical yield; produces glycolaldehyde as intermediate | D-xylose |
| D-ribulose-1-P Pathway | E. coli | Alternative route for pentose utilization; can be combined with other pathways | D-xylose |
The glyoxylate shunt pathway (particularly in E. coli Mgly434) can achieve remarkably high yields of glycolic acid from glucose—up to 90% of the theoretical maximum 1 .
The Dahms pathway shows excellent performance for converting D-xylose to ethylene glycol, with one strain reaching 85% of the theoretical yield 1 .
The transition from laboratory success to industrial production requires addressing multiple challenges, including scaling up processes, improving product purity, and reducing overall costs. Integrated bioprocesses that combine production with efficient recovery methods are essential for commercial viability.
Researchers developed an integrated process using Gluconobacter oxydans to convert ethylene glycol to glycolic acid with remarkable efficiency 3 :
Such high purity is essential for applications in cosmetics and biodegradable polymers, where impurities could cause skin irritation or affect polymer properties. This demonstrates that bioprocesses can compete with, and potentially surpass, traditional chemical processes in both efficiency and product quality.
Despite significant progress, several challenges remain in the widespread adoption of biological production routes for glycolic acid and ethylene glycol. The toxicity of these chemicals to microorganisms at high concentrations limits the maximum achievable titers. Researchers have found that growth of both E. coli and yeasts is significantly inhibited at glycolic acid concentrations above 30-50 g/L, depending on pH 8 .
Integrating computational approaches to predict optimal genetic modifications and process conditions 2
Developing systems where different organisms specialize in different conversion steps for enhanced efficiency
Using adaptive laboratory evolution or synthetic biology to create microbes resistant to product toxicity
Developing pathways with fewer enzymatic steps and higher theoretical yields
"The continuous innovation in formulation and application technologies is expected to drive further market expansion in the coming years" 2 .
The biotechnological production of glycolic acid and ethylene glycol represents a fascinating microcosm of the broader green chemical revolution. By harnessing and reprogramming the metabolic capabilities of microorganisms, scientists are creating sustainable alternatives to traditional petrochemical processes.
Renewable feedstocks replace petrochemical resources
High yields and purity levels competitive with conventional methods
Transforming waste streams into valuable chemical resources
From the elegant pathway engineering in E. coli that links the Dahms pathway with the glyoxylate shunt, to the exploitation of acid-tolerant yeasts like K. lactis, researchers are developing an increasingly sophisticated toolkit for microbial chemical production. The impressive results—with some processes achieving yields exceeding 90% of theoretical maximum and purity levels above 98%—demonstrate that biological approaches can compete with, and potentially surpass, conventional methods.
The story of glycolic acid and ethylene glycol production illustrates how understanding and engineering nature's molecular machinery can help solve some of our most pressing environmental challenges—one microbe at a time.