Sensitive skin is a common problem, affecting approximately 60% of the global population[1]. Individuals with sensitive skin typically have a lower tolerance for irritants in skincare products, triggering adverse reactions such as redness, itching, burning sensations, and inflammation. Therefore, choosing products with safe components is crucial especially for those with sensitive skin.

This trend is also highlighted by data from Grand View Research, which predicts that the global natural and organic cosmetics market will expand to USD 54.5 billion by 2027, growing at a compound annual growth rate of 5.01% from 2020 to 2027[2]. Another trend implied by our survey shows that consumers are increasingly seeking products that are not only effective but also aligned with their growing awareness of health and environmental issues.

Among various types of products, those containing yeast extracts have gained significant popularity. This market concentration has resulted in exorbitant prices for yeast extracts-based products. For instance, the price of yeast extracts product occupied a large share of the market ranges from USD 150 to USD 1000 per 150ml, making these cosmetics largely inaccessible to many consumers.

In addition to the unaffordable cost, the soothing and gentle ingredients for sensitive skin are also in short supply. One such example is (–)-α-Bisabolol. (–)-α-Bisabolol, valued for its anti-inflammatory and antimicrobial properties, is a soothing ingredient in cosmetics for those with sensitive skin. However, extracting (–)-α-Bisabolol from plants is unsustainable and insufficient to meet demand, raising environmental and bioconservation issues[3]. Due to the generation of other diastereomers and unwanted byproducts, chemical synthesis necessitates an extra purification step that is economically unfeasible[4]. For biosynthesis, producing exogenous or endogenous metabolites by engineered bacteria/yeasts is still at risk of cytotoxicity. Notably, a concentration of 1g/L (–)-α-Bisabolol significantly inhibit the growth of yeast, posing a significant challenge[5].

Consequently, there is an urgent need to develop safe, effective, and affordable skincare products by innovative production methods to bridge this gap.

This year, students from iZJU-China proposed an innovative idea to link yeast-derived (Saccharomyces cerevisiae) essence production to an oscillatory system, aiming to reduce the product’s toxicity and increase anti-aging activity during the production process. We have formulated “Yeastea” 2+1 Yeast Extract for comprehensive skin barrier repair. The “2” represents the core ingredients, (–)-α-Bisabolol and ceramides, which work synergistically to enhance anti-inflammatory, calming, and repairing effects. The “1” signifies the yeast extract, rich in diverse beneficial components, aiding in skin repair. By combining these ingredients, we have innovatively crafted the yeast essence “Yeastea” through an integrated production process to address daily skincare concerns.

To address the cytotoxic problem, we have applied the oscillating system in production. By inserting a HAP4-sensitive CYC1 promoter upstream of the SIR2 gene and relocating the HAP4 gene to the 35S rDNA region regulated by SIR2, periodic expression of SIR2 and HAP4 is achieved. By connecting the CYC1 promoter to the ceramide production gene and using the GAL-UAS system to link the expression of SIR2 and (–)-α-Bisabolol production, the oscillator not only helps our experimental yeasts to live longer and produce more ingredients but also helps to avoid the toxicity of excess ingredients.

• Oscillating system

Yeast cells have a genetic switch that can lead to their death through two distinct pathways: nucleolar decline or mitochondrial decay. In yeast, SIR2 mediates chromatin silencing at ribosomal DNA (rDNA) to maintain the stability of this fragile genomic region and the integrity of the nucleolus. HAP4 regulates the expression of genes critical for heme biosynthesis and mitochondrial function. The oscillator was engineered as a negative feedback genetic switch, allowing yeast cells to oscillate between these two states, thereby extending their lifespan by 82%[6].

• Ceramide production

Ceramides, a class of lipid molecules integral to the skin’s stratum corneum, plays a pivotal role in skincare including preventing transepidermal water loss, and shielding against environmental aggressors. They can also mitigate signs of aging by enhancing the stratum corneum’s integrity. However, current extraction methods from natural sources are insufficient to meet the growing demand, and using plants and animals for ceramide extraction is unsustainable.

By overexpressing the TSC10 gene in yeast, which encodes 3-ketodihydrosphingosine reductase—a key enzyme in ceramide synthesis—researchers aimed to maximize ceramide production. Using the pYES2 vector, the TSC10 gene was introduced into the yeast, significantly enhancing ceramide production. The engineered yeast strain, SCYT10, containing the pYES2/TSC10 vector, achieved a ceramide production level of 9.79 mg per gram of yeast cells, which is a 4.7-fold increase compared to the control strain[7]. This theoretical basis demonstrates that overexpressing the TSC10 gene in yeast can significantly boost ceramide production, offering a more sustainable and scalable method for obtaining this essential ingredient in skincare products.

• (-)-α-bisabolol production

(–)-α-Bisabolol is primarily extracted from chamomile (Matricaria recutita) and is valued for the significant potential in health products and pharmaceuticals. However, extracting (–)-α-Bisabolol from chamomiles is unsustainable and insufficient to meet demand. To address this, Saccharomyces cerevisiae was used to produce (–)-α-Bisabolol. By introducing the MrBBS and ERG20 genes, they created a strain that produces (–)-α-Bisabolol de novo. This biosynthesis process uses glucose as a cost-effective carbon source to produce acetyl-CoA, which enters the MVA pathway to create farnesyl pyrophosphate (FPP). FPP is then converted to (–)-α-Bisabolol by the MrBBS enzyme from M. recutita. To further enhance productivity, ERG20 and MrBBS are fused together through a flexible linker (GGGS)3. Therefore, FPP will be immediately captured by MrBBS after it was produced by ERG20. With a result of a 2.9-fold increase in production, this method offers a sustainable alternative to traditional extraction and demonstrates the potential for producing valuable natural compounds at scale[5].

• Fluorescence protein system and microfluidic chip

To indicate the gene expression level, the fluorescence protein system is employed, with BFP used to signify the expression of MrBBS and ERG20 genes. Similarly, enhanced eGFP marks TSC10 expression, while mCherry indicates SIR2 expression.

To evaluate the pattern of oscillating system and address the observation problems caused by suspension culture of Saccharomyces cerevisiae, we use microfluidics chips for single-cell monitoring and imaging applications (see hardware for detailed information)[8]. By using a cell trap of the yeast size (6-micronm diameter), yeast is trapped in the channel. Dot matrix is used as an encoding and calibration standard on microfluidic chip (see software for detailed information). Consequently, a system including a microfluidic chip was adopted to immobilize the yeast cells and enable the assessment of both their oscillating pattern and replicative lifespan.

1. Farage MA. The Prevalence of Sensitive Skin. Frontiers in Medicine [Internet]. 2019;6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533878/

2. Natural Cosmetics Market Size, Share, Trends | Industry Report, 2025 [Internet]. Available from: https://www.grandviewresearch.com/industry-analysis/natural-cosmetics-market

3. de Souza AT, Benazzi TL, Grings MB, Cabral V, Antônio da Silva E, Cardozo-Filho L, et al. Supercritical extraction process and phase equilibrium of Candeia (Eremanthus erythropappus) oil using supercritical carbon dioxide. The Journal of Supercritical Fluids. 2008 Dec 1;47(2):182–7.

4. Son YJ, Kwon M, Ro DK, Kim SU. Enantioselective microbial synthesis of the indigenous natural product (−)-α-bisabolol by a sesquiterpene synthase from chamomile (Matricaria recutita). Biochem J. 2014;463:239–48.

5. Jiang Y, Xia L, Gao S, Li N, Yu S, Zhou J. Engineering Saccharomyces cerevisiae for enhanced (–)-α-bisabolol production. Synthetic and Systems Biotechnology. 2023 Jun 1;8(2):187–

6. Zhou Z, Liu Y, Feng Y, Klepin S, Tsimring LS, Pillus L, et al. Engineering longevity—design of a synthetic gene oscillator to slow cellular aging. Science. 2023 Apr 28;380(6643):376–81.

7. Sk K, Yh N, Jr K, Hs Y. Effect of expression of genes in the sphingolipid synthesis pathway on the biosynthesis of ceramide in Saccharomyces cerevisiae. Journal of microbiology and biotechnology [Internet]. 2010 Feb; 20(2). Available from: https://pubmed.ncbi.nlm.nih.gov/20208441/

8. A programmable fate decision landscape underlies single-cell aging in yeast | Science [Internet]. Available from: https://doi.org/10.1126/science.aax9552