Salidroside, a natural product known for its anti-hypoxia, anti-oxidation, anti-inflammatory, anti-aging, and anti-tumor properties, is extensively utilized in the food, cosmetics and pharmaceutical industries. Traditionally, salidroside has been obtained through the extraction from the rhizomes and tubers of Rhodiola species, including water extraction, two-phase aqueous extraction, supercritical CO₂ extraction and microwave assisted extraction. However, its low natural abundance (with the salidroside content in rhizomes and tubers of Rhodiola species ranging from 0.5% to 0.8%), coupled with escalating demand, has led to a progressive depletion of these plant resources. Given the broad application potential of salidroside, the rapid growth of market demand, and the increasing scarcity of natural resources, there is an urgent need to develop innovative synthetic approaches for this valuable compound. Chemical synthesis of salidroside is characterized by its efficiency and rapid processing time. However, the use of strong acids, bases, and catalysts with heavy metal ions in the synthesis process poses challenges for the separation of salidroside with environmental risks. In recent years, with the advancements in synthetic biology, the construction of microbial cell factories for the biosynthesis of salidroside has become a viable strategy for addressing the current supply-demand imbalance and resource scarcity associated with the natural biosynthetic pathway of salidroside. To enhance the production of salidroside biosynthesis, two major strategies can be employed. First, metabolic engineering approaches can be used to overexpress key genes in the synthesis pathways while knocking out or downregulating the expression of genes related to the bypass routes, thereby increasing precursor accumulation and enhancing the metabolic flux. Second, enzyme engineering can be applied to improve the catalytic efficiency and regioselectivity of natural glycosyltransferases, which often exhibit low activity and poor selectivity. Sequence alignment techniques can be used to identify and screen potential glycosyltransferases from various biological genomes. Additionally, protein engineering combined with computational approaches can be utilized to optimize these enzymes to meet specific requirements, ultimately improving the production of salidroside. In this comprehensive review, we systematically assess the pharmacological activities of salidroside, the plant biosynthetic pathway, the mining and screening of the enzymes, and the biosynthetic advancements in Escherichia coli and Saccharomyces cerevisiae. Additionally, we discuss the separation and purification methods of salidroside and its application potential as a synthetic intermediate in the preparation of other compounds, such as hydroxysalidroside, verbascoside and echinacoside. This review aims to enhance the understanding of the biosynthetic pathway of salidroside, thereby promoting a greener and more efficient biosynthetic approach to salidroside production.

With the rapid growth of consumption in cosmetics, demand for their raw materials is expanding correspondingly, which not only drive the efficacy and product competitiveness but are also crucial for ensuring safety. Synthetic biology, an emerging interdisciplinary field based on engineering principles, leverages gene editing, computer simulation, and bioengineering technologies to design, modify, and even resynthesize organisms through rational strategies. Saccharomyces cerevisiae, an important microbial platform, is increasingly used in the production of cosmetic raw materials. Constructing S. cerevisiae cell factories for the heterologous biosynthesis of cosmetic ingredients presents an eco-friendly and sustainable alternative to traditional plant extraction and chemical synthesis, addressing both environmental concern and resource limitation. In this article, we review the development of gene editing technology and its key role in constructing biosynthetic pathways for the production of cosmetic raw materials with S. cerevisiae. We also summarize the application of metabolic engineering strategies such as multi-copy gene integration, compartmentalization, transporter engineering, and multicellular system in the optimization of S. cerevisiae cell factories. Moreover, we present the latest progress in the biosynthesis of different cosmetic active ingredients with S. cerevisiae cell factories, such as terpenes, vitamins, polyphenols, proteins and amino acids. While the potential and advantages of using S. cerevisiae for large-scale production of cosmetic raw materials are significant, a series of challenges remain, including incomplete biosynthetic pathway analysis, low biosynthesis yield, and low yield with the separation and purification. Looking ahead, the integration of artificial intelligence, machine learning, and other advanced technologies is expected to establish more efficient gene editing tools for the optimization of yeast cell factories and the biosynthesis of cosmetic raw materials, providing technical support and practical guidance for the sustainable development of the cosmetics industry.

Functional peptides are short chain peptides composed of 2 to 50 amino acids, and their biological activities are closely related to their amino acid sequences, chain length, and structural architectures. Functional peptides can play a regulatory role in a variety of physiological processes by specifically recognizing and binding to target molecules in vivo. Due to their rapid action, strong specificity, less side effect and toxicity, functional peptides have shown great application potentials in many fields such as biomedicine, food science and cosmetics. For example, in the field of biomedicine, functional peptides can be used as the basic material of antimicrobe, anticancer, immune regulation and other therapeutic factors. In the food industry, they are used as natural supplements to enhance nutritional value for health benefit. In the field of cosmetics, functional peptides are widely used for the anti-aging, moisturizing, and repairing of the skin. In this paper, we discuss the ways of obtaining functional peptides, mainly including protein hydrolysis, chemical synthesis, and biosynthesis (e.g., through microbial recombinant expression technology), and compare their advantages and disadvantages and respective application scenarios. In terms of strategies for mining functional peptides, we review the latest research progress including phage surface display, machine learning algorithm, molecular docking and artificial intelligence. These techniques show significant potentials in the screening and design of functional peptides. In recent years, the rapid development of synthetic biology and the wide applications of bioinformatics and artificial intelligence have provided new ideas and strategies for the discovery and optimization of functional peptides, making it possible to screen functional peptides through machine learning and high throughput. Looking forward to the future, the research of functional peptides will face new challenges and opportunities. Improving the synthesis process for high efficiency, improving the stability of functional peptides through structural modifications, and using computer-aided optimization and artificial intelligence to design multifunctional peptides will become important research directions. At the same time, strengthening the safety and efficacy assessment of functional peptides can further enhance the applications of functional peptides.

The development of synthetic biology has witnessed rapid advancements, which have significantly promoted production innovations in multiple sectors. In the cosmetics industry, the production methods of amino acid derivatives, which are a kind of pivotal raw materials in cosmetics, are experiencing groundbreaking innovations. The traditional methods for the production of amino acid derivatives have the problem of high cost, and usually generate environmental risk. Besides, the production stabilities of the target products are often unsatisfactory. The application of synthetic biology technology in the design and engineering of microbial cell factories for the bioproduction of amino acid derivatives, can greatly enhance the production efficiency and reduce the production costs of the target products. This innovative approach not only enhances the development of green biomanufacturing, but also benefits the demand of market for natural, safe, and functional cosmetic ingredients. In this review, an overall introduction to the utilization of amino acid derivatives in cosmetics industry is first provided. Subsequently, the strategies for the construction of high-producing strains for the production of amino acid derivatives are comprehensively summarized, which are basically categorized into two groups: enzyme conversion and microbial fermentation. The application of enzyme engineering, rational metabolic engineering, and random screening in the construction of microbial cell factories for the production of amino acid derivatives are systematically introduced. Moreover, the current research advancements and trends in the biosynthesis of amino acid derivatives as cosmetic raw materials are outlined. With the support of the cutting-edge technologies such as artificial intelligence, synthetic biology will further promote the production innovation process, enabling efficient and eco-friendly biomanufacturing of a wider array of cosmetic raw materials. This ongoing evolution holds immense promise for the cosmetics industry, promising a future with sustainable and innovative products.

The demand for personal care products has been increasing steadily. Consumers are now seeking for products that offer enhanced functionality, natural ingredients, and superior feeling experiences. Fragrances and flavors are key components in personal care formulations. Terpenes and their derivatives dominate natural fragrances due to their diverse structures and scents, widespread availability from plants and animals, stable function, and high safety profile. The terpene fragrance market is projected to grow at an annual growth rate of 6.4%, reaching $1.01 billion by 2028, indicating a high market revenue and promising future. Currently, the acquisition of natural terpene fragrances is constrained by the long growth cycle of plants, low terpene content, and high extraction cost. Thus, there is an urgent need for developing new technology, such as synthetic biology, to achieve large-scale production of diverse fragrance compounds at an environment-friendly manner. This review explores the application and development of synthetic biology in the sustainable production of terpene fragrances, highlighting how data-driven synthetic biology and biotechnological innovations empower terpene fragrance production. It also compares classical and alternative terpenoid biosynthesis pathways, elucidating their differences and advantages, which can offer comprehensive insights for chassis design toward terpenoid efficient biosynthesis. Additionally, this review explores recent advances in terpene synthase discovery and engineering as well as cell factory construction. Furthermore, we comprehensively summarizes challenges encountered in the construction of three major types of terpene fragrance cell factories: monoterpenes, sesquiterpenes, and nor-isoprenoids, and discusses metabolic engineering strategies that can be employed to address these issues, including enzyme optimization, pathway reconstruction, and cellular detoxification. At the end, we comment the current landscape of patents and industrial competition, offering insights into future challenges and opportunities, including the hurdles of biosynthesis technology, the discovery and design of new products, as well as the market regulation and safety concerns.

Yeast mannoprotein is a non-fibrous glycoprotein localized on the outermost layer of yeast cell walls. As a natural functional ingredient, its commercial application is limited and currently only used as a wine stabilizer. To advance the development and broader commercialization of mannoprotein, this paper briefly outlines its structural characteristics, including the peptide chain, core region, and outer chain composition. The peptide chain forms the backbone of mannoprotein, while the core and outer chains are composed of various carbohydrate portions, predominantly mannose residues. This unique structure contributes to the diverse biological activities of mannoprotein. The advantages and disadvantages of acid, alkali, enzyme, and physical methods for extracting yeast mannoprotein are discussed. Acids and bases are effective for extracting yeast mannoprotein, but may compromise its structural integrity, while enzymatic extraction is less destructive, preserving the structure but with a higher cost. A systematic review is conducted on the biological activities of yeast mannoprotein in improving intestinal health, stimulating immunity, antioxidation, lowering blood lipids, and adsorbing mycotoxins, as well as its applications in the production of oligosaccharides, bio emulsifiers, nutritious and healthy foods, fruit preservation, animal nutrition, and wine production. Finally, research progress on the synthesis pathways of N-glycosylation and O-glycosylation in yeast mannoprotein and strategies for controlled gene modifications provide new technologies for efficient production of mannoprotein. Despite these advances, the production and application of yeast mannoprotein still face challenges. The diversified structures of yeast mannoprotein pose challenges to research. The action mechanism, spatial structure, molecular weight, and interrelationship of yeast mannoprotein are not fully understood. Future research should focus on elucidating the relationship between the structure of yeast mannoprotein and its biological activity. Combined with the application of biosynthesis technology, it is expected to promote the development of the yeast mannoprotein industry and enhance its applications in fields such as foods, cosmetics, medicines, etc.

Flavonoids are natural ingredients commonly used in cosmetics, mainly for their antioxidant and anti-inflammatory effects, but they also present a variety of other biological activities such as antimicrobial, whitening, and anti-ultraviolet. Therefore, flavonoids have a huge application potential waiting to be explored. In this review, firstly, the numerous biological properties of flavonoids used in cosmetics, as well as examples of their applications in cosmetics are presented, with their biosynthetic pathways addressed. Then, recent advances in biosynthesis of typical flavonoids (e.g., phloretin, naringenin, apigenin, luteolin, chrysin, rutin, and anthocyanins) are reviewed and discussed, with a focus on the novel synthetic biology and metabolic engineering strategies to improve the productivity and yield of biosynthesized flavonoids, including the enhancement of precursor supply, characterization and modification of key enzymes, regulation of gene expression, and optimization of fermentation processes. With the continuous innovation of synthetic biology technology, there has been an increase in the efficiency of flavonoid biosynthesis and a significant reduction in production cost, which contributes substantially to the widespread use of flavonoids in cosmetics. However, the prevalence of poor solubility and low stability of flavonoids limits their applications in cosmetics. To address this issue, we outline the research process of two main strategies: nanocarrier technology and moiety modification. The application of these research results opens up new possibilities for the use of flavonoids in cosmetics. At the end, we discuss two major challenges in high-yield synthesis of complex flavonoids: the difficulty of key enzyme modification and the imbalance of metabolic flux. We also look forward to AI-assisted synthetic biology to address these challenges and drive the yield improvement and industrialization of flavonoid biosynthesis, providing biotechnological power for the development and innovation of the cosmetics industry.

Hyaluronic acid (HA), a natural linear acidic polysaccharide composed of disaccharide units of D-glucuronic acid (D-GlcA) and N-acetylglucosamine (N-GlcNAc), has been widely used in the cosmetic and medical fields. HAs with different molecular weights exhibit distinct biophysical properties. While high molecular weight HAs have stronger viscoelasticity and resistance to degradation, low molecular weight HAs demonstrate enhanced biological functions. Significant progress has been made for the industrial production of HAs, with the shift from traditional extraction from animal tissues to microbial fermentation. However, the use of the natural HA-producing species Streptococcus zooepidemicus presents challenges, such as potential pathogenicity and difficulties in molecular modifications, which limit the study on the biosynthesis of HAs with varying molecular weights. Recently, the increasing demand for specific molecular weight HAs has driven the application of metabolic engineering and synthetic biology techniques for their biosynthesis and molecular weight regulation. By identifying the key factors involved in the processes, researchers have developed various strategies to optimize the synthesis of HAs and control their molecular weights. This article first analyzes the limiting factors in the synthesis of medium and high molecular weight HAs, focusing on the genetic regulation on the synthesis pathways of HA precursors and the weakening of competitive branches. Secondly, it discusses the impact of HA synthase, precursor supply, and fermentation conditions on the synthesis of ultra-high molecular weight HAs. Finally, it summarizes the preparation strategies for low molecular weight HAs, including physical and chemical methods, enzymatic methods, and microbial direct fermentation as well. The review summarizes the latest research progress regarding challenges faced in the biosynthesis and molecular weight regulation of HAs: specifically, the insufficient molecular weight of high molecular weight HAs, the weak synthesis capability of medium molecular weight HAs, and the poor controllability of low molecular weight HAs. It provides a systematic overview on enhancing the understanding of strategies for HA biosynthesis and molecular weight regulation, aiming to facilitate the efficient biosynthesis of HAs with controlled molecular weights.