The urgent global demand to reduce sugar calorie intake has driven a boom in alternative sweeteners. Natural sweeteners—compounds derived from plants or engineered through biosynthesis—offer a way to satisfy human sweet taste receptors while mitigating the metabolic, dental, and glycemic drawbacks of sucrose.

At Alfa Chemistry, we provide natural sweeteners directly from plants that help you satisfy your sweet tooth and are also good for your health. Browse our range of high-purity, research-grade natural sweeteners below:
For a complete product assortment and technical details, please refer to our product catalog or contact our team.
Overall, natural sweeteners are better aligned with the "clean label" and "green chemistry" principles than many synthetic high-intensity sweeteners. However, the design and development of natural sweeteners require chemical biology expertise: from the receptor binding and metabolism to biosynthetic pathways and formulating the product. In this article, we will give you a technical insight into natural sweeteners, from their molecular design and production strategies to regulatory issues and industrial upgrading.
Molecular Diversity of Natural Sweeteners
Natural sweeteners can be broadly categorized into the following chemical families.
Class | Representative Examples | Relative Sweetness vs Sucrose | Key Features / Challenges |
Terpenoid glycosides | Steviol glycosides (stevioside, Rebaudioside A), mogrosides | 30–300× (steviol glycosides), ~250× (mogrosides) | High stability, but sometimes bitter or lingering aftertaste |
Polyols (sugar alcohols) | Erythritol, xylitol, sorbitol, mannitol | ~0.6–1.0× (bulk) | Provide bulk and sweetness but may induce osmotic effects or laxation at high dose |
Sweet proteins / peptides | Thaumatin, monellin, brazzein | 500–2000× (brazzein), ~2000× (thaumatin) | Very potent, but often challenging to express and purify at scale |
Flavonoids / Dihydrochalcones | Neohesperidin dihydrochalcone (NHDC), phlorizin derivatives | up to ~1500× (NHDC) | Excellent as taste modulators, but slow onset or lingering aftertaste, sometimes synergy with other sweeteners |
Other natural small molecules | Glycyrrhizin (licorice derivative), hernandulcin | ~30–100× (glycyrrhizin), >1000× (hernandulcin) | Sweet but may impart licorice flavor or bitter undertones; regulatory hurdles exist |
Sweet taste perception originates from binding to the heterodimeric receptors TAS1R2/TAS1R3 in human taste buds. As you can see, each of the sweetener classes above has a unique mode of interaction with the human sweet receptor and different formulating pros and cons.
Figure 1. The main pathway of taste transduction. After sweeteners bind to T1R2/T1R3 receptors, the heterotrimeric G protein dissociates, leading to enhanced phospholipase C-β2 activity, which in turn causes the release of intracellular calcium ion stores mediated by inositol 1,4,5-triphosphate (IP3) receptor type 3 (IP3R3). The last component of the transduction mechanism is the transient potential ion channel TRPM5, whose opening leads to membrane depolarization[1].
Natural sweeteners must bind to and stabilize the receptor in its active conformation. Structural determinants include hydrogen-bonding networks, hydrophobic interactions, the sugar moiety, and conformational flexibility. For example, steviol glycosides contain multiple glucose units that form hydrogen bonds with receptor residues, helping to modulate affinity and off-rate kinetics. Variations in sugar linkages can adjust the balance of sweetness and bitterness.
In terms of formulation, onset (how quickly the sweetness is perceived) and persistence (aftertaste) need to be balanced. Some compounds such as NHDC have low onset, but high persistence can be addressed by blending with other compounds or by the use of adjuvants.
Figure 2. Main steviol glycosides originating from steviol, the basic aglycone unit[2].
Biosynthesis of Natural Sweeteners
Directly extracting sweet compounds from plants typically results in low yields, high costs, and challenges in large-scale, sustainable production. Over the past decade, synthetic biology has emerged as a powerful tool for producing natural sweeteners in microbial or cell culture systems.
Figure 3. Stevioside biosynthesis pathway (MEP pathway) in Stevia rebaudiana[3].
Alfa Chemistry describes some key enzymatic pathways for natural sweetener classification below.
Terpenoid Glycosides
The core precursors are isopentenyl pyrophosphate (IPP)/dimethylallyl pyrophosphate (DMAPP), derived from sources such as the MVA (mevalonate) or MEP (methylerythritol phosphate) pathways. These building blocks condense to form the backbones of diterpenoids (such as steviol) or triterpenoids (such as the precursor to glycyrrhizin). Glycosyltransferases then attach glycosyl moieties (glucose, rhamnose, etc.) to the sugar groups. In the case of stevioside, UDP-glucosyltransferases (UGTs) catalyze the sequential glycosylation of steviol to stevioside/rebaudioside A.
Sweet Proteins
For small proteins like brazzein, current research focuses on heterologous expression in microbial substrates (e.g., E. coli) or plants, utilizing signal peptides and folding aids. Brazzein is thermostable and suitable for recombinant production. Downstream purification and formulation (e.g., refolding, glycosylation control) remain key bottlenecks.
Polyol Production
Enzymatic reduction of sugar precursors (e.g., glucose to sorbitol) or fermentation-based production (e.g., yeast or bacteria converting sugar to erythritol) are well-established. Optimizing flux, cofactor balance, and product output through strain engineering is a current research focus.
Figure 4. General scheme for the biosynthesis of terpenoids[4].
Challenges and Optimization Strategies
- Pathway Balance: Overexpression of an enzyme may lead to metabolic imbalance, substrate depletion, or toxicity. The use of dynamic regulation, feedback control, or flux sensors is crucial.
- Enzyme Promiscuity and Specificity: Side reactions may produce undesirable glycosides or isomers. Directed evolution and protein engineering can improve specificity.
- Product Toxicity/Export: Accumulated sweeteners may inhibit host growth; engineering of transporters or secretion systems may be necessary. Scalability and Yield: Achieving industrial-scale yields (a few to tens of grams per liter) at acceptable purity and cost remains a challenge.
- Regulatory and Safety Considerations: For novel biosynthetic compounds, regulatory agencies require toxicology, stability, and purity data.
Functionality, Stability, and Formulation Behavior of Natural Sweeteners
Natural sweeteners need to perform just as well or better than other categories on all stages of the value chain beyond sweetness itself: production, storage and sensory.
Heat Stability, pH, and Storage Stability
Many terpenoid glycosides (e.g., steviol glycosides and mogrosides) exhibit excellent heat and acid stability, making them suitable for pasteurized and shelf-stable beverages. Sweetening proteins like brazzein are pH stable (range 2.5-8) and can be heated for extended periods (98°C/2hrs). Dihydrochalcones like NHDC are also stable over a wide pH range and shelf life and may be used as an additive in acidic beverages.
Synergy and Blending Effects
Blending multiple sweeteners can create desirable synergistic effects—reducing costs, masking bitterness, and improving sweetness. For example:
- NHDC is generally used in very low doses alongside another sweetener(s) to "enhance sweetness." This system reduces bitterness and increases sweetness.
- Sweetening proteins may help reduce the off-flavors of glycosides or polyols. Bulk polyols have a rich mouthfeel lacking in most high-intensity sweeteners.
Taste Kinetics: Onset and Persistence
Sweetness kinetics are crucial: sugar is perceived quickly and dissipates quickly, while many natural sweeteners have a slower onset and a poorer persistence. Taste engineers can adjust this through blending ratios, flavor modifiers, or masking agents.
Caloric and Metabolic Behavior
- Most natural sweeteners do not cause a spike in blood sugar: the human body does not produce the digestive enzymes to cleave glycosides (such as steviol glycosides), so the glycoside is excreted unchanged or eliminated from the body.
- Polyols contribute some caloric value (e.g., 0.2–2 kcal/g, depending on the amount absorbed).
- Some compounds (e.g., glycyrrhizic acid) may interact with metabolism or have mineralocorticoid effects, requiring careful dosage control.
Industry Transformation and Market Landscape
Consumers demand not only sweetness but also safety, label transparency, and functionality (e.g., stability, mouthfeel). Industry trends include:
- "Hybrid sweetener systems" combining polyols, glycosides, and proteins to optimize taste and reduce costs.
- Precision fermentation and microbial platforms to reduce production costs.
- High-throughput screening and enzyme engineering to discover new sweeteners or improve existing ones.
- Cross-jurisdictional regulatory harmonization to streamline international product launches.
Frequently Asked Questions (FAQs)
1. What makes a sweetener "natural" rather than synthetic?
A natural sweetener is typically derived from botanical sources or produced via biological (microbial) processes, rather than fully synthetic chemical routes. It often shares provenance from plants or natural metabolic pathways.
2. Why not just use stevia or monk fruit for all sweetening needs?
A: While stevia (steviol glycosides) is broadly used, it has limitations: lingering aftertaste, moderate sweetness, and formulation compatibility. Other sweeteners (e.g., sweet proteins, NHDC) may help fill gaps in onset, flavor, or cost.
3. Are natural sweeteners safe for diabetics?
Many natural sweeteners are non-glycemic and don't spike blood glucose, making them suitable for diabetics. But safety also depends on dose, metabolic byproducts, and individual tolerance.
4. Can natural sweeteners fully replace sugar in baking or cooking?
Not always. Sugar provides bulking, browning (Maillard reactions), and physical structure (crystallinity) that many alternatives can't replicate. Often, blends or specialized formulation strategies are required.
5. Why are natural sweeteners so expensive compared to sugar?
Low natural abundance, complex purification, enzyme pathway inefficiencies, and regulatory costs contribute to high price. Advances in synthetic biology aim to reduce these costs.
6. How long before a novel sweetener gains regulatory approval?
It can take several years of toxicology, pilot manufacturing, regulatory review (e.g. GRAS, EFSA novel food), and consumer trials before market approval.
7. Do natural sweeteners have an aftertaste or bitterness?
Many do: glycosides may leave bitterness or lingering "cool" notes; sweet proteins may have delayed onset. Taste engineers mitigate these via blending, masking agents, and kinetics tuning.
8. Are there risks or side effects to consuming natural sweeteners?
At high dosages, polyols may cause gastrointestinal discomfort (e.g., osmotic effects). Unverified compounds may carry unknown metabolic or allergic risks, which is why toxicology is critical.
References
- Jain A., et al. What Does Diabetes "Taste" Like? Current Diabetes Reports. 2016, 16(6), 49.
- Srivastava V., et al. An interdisciplinary approach towards sustainable and higher steviol glycoside production from in vitro cultures of Stevia rebaudiana. Journal of Biotechnology. 2022, 358, 76-91.
- Ghaheri M., et al. Study of gene expression and steviol glycosides accumulation in Stevia rebaudiana Bertoni under various mannitol concentrations. Molecular Biology Reports. 2019, 46(10), 7-16.
- Brocksom T., et al. The Chemistry of the Sesquiterpene Alkaloids. Journal of the Brazilian Chemical Society. 2017, 28(6).
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