In the fierce competition of the cosmetics raw material market, amino acid derivatives have become the new favorite of the market due to their excellent effects in anti-aging, moisturizing, repairing, and whitening. However, the many drawbacks of traditional production methods make it difficult for them to fully utilize their strengths and weaknesses. Nowadays, using synthetic biotechnology to build "microbial cell factories" can not only improve the production efficiency and reduce production costs of amino acid derivatives, but also achieve green manufacturing. Professor Xie Xixian's team from the School of Bioengineering at Tianjin University of Science and Technology has been committed to research in this field for a long time. Their latest article, "Application of Amino Acid Derivatives in Cosmetics and Research Progress on Their Biological Synthesis," systematically elaborates on the application prospects of synthetic biotechnology in the production of amino acid derivatives, opening up a new path for the production of cosmetic raw materials. Amino acids are the basic units that make up proteins, and amino acid derivatives are compounds obtained by modifying the structure of amino acid molecules through chemical or biological methods. ”Xie Xixian explained that this modification may involve introducing functional groups such as hydroxyl and acyl groups, or altering the molecular structure. Compared to single amino acids, amino acid derivatives have richer physiological activities and superior application performance, which is also the key to their standing out in the cosmetics field, "said Xie Xixian. In terms of skincare efficacy, amino acid derivatives can be called "versatile". Xie Xixian gave an example to introduce: "As one of the amino acid derivatives, glutamic acid derivatives have outstanding moisturizing ability, can lock skin moisture like a sponge, and are the core component of many moisturizing facial mask and lotion; aromatic amino acid derivatives have antioxidant and anti-inflammatory properties, which can not only resist free radical damage caused by ultraviolet rays, delay the process of skin aging, but also inhibit the activity of enzymes related to melanin production, and help whitening." In addition, some amino acid derivatives can also promote the repair of skin cuticle and enhance the skin barrier function. However, such high-quality raw materials faced production bottlenecks before the rise of synthetic biotechnology. Associate Professor Ma Qian from the School of Bioengineering at Tianjin University of Science and Technology introduced that there are mainly two types of traditional methods for producing amino acid derivatives: one is to extract and isolate specific amino acid derivatives from natural resources, such as animal and plant tissues; The second is through chemical synthesis, using chemical raw materials to react under harsh conditions such as high temperature and high pressure. These production methods have obvious shortcomings. ”Ma Qian bluntly stated that natural extraction methods rely on resource abundance, with extremely low yields and high costs. For example, some rare amino acid derivatives may only extract a few grams of target substances per ton of natural raw materials, which cannot meet the production needs of cosmetics. Although chemical synthesis methods can increase production, they require a large amount of fossil raw materials and produce toxic and harmful wastewater and exhaust gas during the reaction process, which is not environmentally friendly and may result in residual chemical impurities in the products that affect the safety of cosmetics. More importantly, the stability of amino acid derivatives produced by traditional methods is poor, and the efficacy of different batches of products fluctuates greatly, which makes cosmetics companies quite cautious in their raw material selection. The emergence of "microbial cell factories" and "synthetic biotechnology" is equivalent to equipping the production of amino acid derivatives with an "intelligent engine". ”Xie Xixian metaphorically states that the core is to design and construct a "microbial cell factory" - transforming microorganisms into miniature chemical plants, allowing them to produce target products in a targeted and efficient manner. How to operate it specifically? The research conducted by Xie Xixian's team has provided a clear path. Firstly, it is necessary to 'draw a blueprint', that is, to analyze the natural synthesis pathway of the target amino acid derivative, or to design a more efficient artificial synthesis pathway from scratch. For example, if we want to produce a rare amino acid derivative - ergothionein, we need to figure out its synthesis steps in certain fungi and which enzymes work in it, "said Xie Xixian. Next is' building a factory ', which uses gene editing tools such as CRISPR to introduce key genes responsible for catalytic reactions into chassis microorganisms such as Escherichia coli and brewing yeast, while inhibiting the bypass metabolism of microorganisms that consume raw materials, ensuring that the nutrients consumed by microorganisms are converted into target products as much as possible. Finally, it is about 'production', providing low-cost carbon sources such as glucose for the modified microorganisms in the fermentation tank, and controlling temperature, pH, and other conditions to allow them to 'work hard' in a mild environment and synthesize the target product in large quantities. Compared to traditional methods, this production method can be considered to have disruptive advantages. Efficiency and cost are the most intuitive breakthroughs. ”Xie Xixian gave an example that the team once optimized the production path of ergothionein through synthetic biotechnology, which increased its fermentation yield from milligrams per liter in the past to the level of grams per liter, achieving a breakthrough in scale. This means that the cost has significantly decreased, and ingredients that were originally only used for high-end products now have the opportunity to be used for ordinary products, "said Xie Xixian. In terms of environmental protection, synthetic biotechnology is a "green benchmark". Microorganisms can use biomass materials such as corn for production, without relying on fossil resources; the reaction can be carried out at room temperature and pressure, with low energy consumption and almost no pollution. "Xie Xixian emphasized that this fully meets the cosmetics industry's pursuit of natural, safe, and sustainable products. In addition, the biosynthetic technology for producing amino acid derivatives also ensures their safety and purity. The traditional production method using animals and plants as raw materials may result in the final product being mixed with substances that may cause human infections or allergic reactions due to the presence of pathogens or specific proteins in the raw materials themselves. However, the closed fermentation system used in synthetic biotechnology can cut off such risks from the source. At the same time, genetic regulation can also reduce by-products, making the product more pure and effective. Xie Xixian added that what is more exciting is that synthetic biotechnology can also design new synthetic pathways to produce amino acid derivatives that do not exist in the natural world but have better efficacy, opening up unlimited space for innovation in cosmetic raw materials. The large-scale application requires breaking through multiple barriers. Nowadays, amino acid derivatives produced by synthetic biotechnology have accelerated from laboratory samples to consumers' dressing tables. Ergothionein is a typical example. ”Xie Xixian introduced that this amino acid derivative has become a standard configuration for high-end anti-aging lines of major brands due to its strong antioxidant capacity. Many products are intentionally labeled as' synthetic biological sources' to highlight the high quality and technological sense of the raw materials, "said Xie Xixian. Recombinant collagen is another major "star" product. Compared with traditional animal derived collagen, recombinant collagen produced by synthetic biotechnology is more compatible with human sequences, has no viral risk, and has good biocompatibility. "After the relevant products were launched, they quickly occupied the market. Now many medical beauty facial mask and repair essence contain recombinant collagen," Xie Xixian said. In addition, amino acid derivatives such as gamma aminobutyric acid with anti sensitivity, tetrahydropyrimidine with anti stress moisturizing properties, and gamma polyglutamic acid with long-lasting water locking properties have also been mass-produced through synthetic biotechnology and become commonly used raw materials for functional cosmetics. It can be said that the market for amino acid derivatives driven by synthetic biotechnology is in a period of rapid growth. ”Ma Qian pointed out that there are still several hurdles to overcome in order to achieve larger scale and lower cost applications of amino acid derivatives. The first challenge is the optimization of the chassis strain. The ideal 'cell factory' needs to have clear metabolic pathways, genetic stability, and strong stress resistance, but many natural production strains are difficult to modify. At the same time, commonly used E. coli and yeast are prone to 'fatigue' when expressing complex synthetic pathways - excessive metabolic burden can lead to slower growth, reduced products, and even death due to product toxicity. "Ma Qian admitted that how to make strains' more capable and durable 'is currently the research focus of the team. Next is the performance bottleneck of key enzymes. Enzymes in the synthetic pathway are like workers on a production line, but many natural enzymes are either 'selective' - substrate specificity is too strong, or 'inefficient' - catalytic reactions are slow, and even 'don't know how to work' - the mechanism of action is unclear. "Ma Qian explained that although gene editing can optimize enzyme performance, it is extremely difficult to simultaneously improve its activity, stability, and expression level, which is one of the core obstacles limiting the increase in product yield. The amplification effect from the laboratory to the factory cannot be ignored again. During the small-scale experiment, the strain performed well, but when placed in a large fermentation tank weighing tens of tons, it may not be suitable for the environment. "Ma Qian gave an example that uneven distribution of oxygen, temperature, and pH values in the large tank may lead to metabolic disorders in microorganisms. How to optimize the fermentation process and ensure that the yield and stability of large-scale production are consistent with those of small-scale trials is a key challenge for industrialization. In addition, research and purification costs also need to be controlled. The early development of bacterial strains requires a repeated cycle of 'design build test learn', which is time-consuming and labor-intensive; the purification steps of fermented products are complex, and the cost often accounts for more than half of the total cost. Ma Qian believes that in the future, automated design tools need to be used to shorten the research and development cycle and develop more efficient purification technologies in order to further reduce costs. Despite the numerous challenges, experts remain confident in the application prospects of synthetic biotechnology in the production of amino acid derivatives. They believe that with the advancement of gene editing technology and optimization of fermentation processes, these challenges will gradually be overcome. Xie Xixian and Ma Qian both believe that synthetic biotechnology will not only provide more safe and efficient raw materials for the cosmetics industry, but also promote the transformation of the entire beauty industry towards a green and sustainable direction. In the future, every bottle of skincare products used by consumers may embody the wisdom of synthetic biotechnology, which is the driving force of technological progress for a better life. ”Xie Xixian stated. (New Society)