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.

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.

L-arginine is an alkaline amino acid that has been used as a neutralizer, moisturizer, and antioxidant in skin care products. In addition, L-arginine is also widely used in feed, medicine, and food industries. The wide range of applications for L-arginine has garnered significant attention for its robust production. L-arginine can be produced through protein hydrolysis and microbial fermentation. However, protein hydrolysis has drawbacks, including complicated operation, high purification cost, low recovery efficiency, and environmental pollution. In contrast, the microbial fermentation can use renewable and cheap feedstock. Besides, the process is performed under mild conditions, and thus is more environmentally friendly. At present, engineered microorganisms such as Corynebacterium glutamicum and Escherichia coli are major producers of L-arginine, and design and construction of microbial strains is the robust production of L-arginine through microbial fermentation. Random mutagenesis and screening strategies are used to develop L-arginine producing microbial strains, which are random with uncertainties, resulting in a low-efficiency for the breeding. With the development of synthetic biotechnology, development of L-arginine producing strains is empowered by the rational design of artificial synthetic pathways and regulatory machineries, taking advantages of advanced genome editing technologies. This paper reviews the progress in the studies of the synthetic pathways and regulatory mechanisms of L-arginine production that have been discovered in different microorganisms. Synthetic biology-guided metabolic engineering strategies for improving L-arginine production in C. glutamicum and E. coli are summarized. Besides, the application of the biosensor-based high-throughput screening strategy for selecting L-arginine producing strains is introduced. Finally, potential strategies to enhancing L-arginine production and the possibility of using new carbon resources such as non-food biomass and one-carbon feedstock for L-arginine production are discussed. It is envisioned that synthetic biology-guided strain engineering will further enhance the production of L-arginine, particularly using non-food feedstock in the near future.

Mycosporine-like amino acids (MAAs), a class of natural sunproof molecules, have attracted intensive attention because of their potent ultraviolet (UV) -absorbing capabilities and potential applications in the cosmetics industry. However, the complicated extraction process and low yield restrict their applications. To address challenges with the supply of MAAs, reconstructing the biosynthesis pathway for their production in microbial cells with synthetic biology techniques provides an effective strategy. This article systematically reviews current progress in the biosynthesis of MAAs, covering a range of critical aspects, including the analysis of structural diversity, which is essential for understanding the functional properties of different MAAs. Additionally, the article delves into the elucidation of biosynthetic pathways, providing insights into the biochemical steps and enzymes involved in the production of MAAs. Furthermore, this review explores the construction of chassis cells in the biosynthesis of MAAs, including the integration of heterologous genes and the optimization of metabolic pathways, highlighting the importance of selecting and engineering suitable microbial hosts to optimize MAAs biosynthesis. The review provides a forward-looking perspective on microbial synthesis of MAAs, with a focus on driving innovation in green and efficient biomanufacturing of these high-value compounds. Meanwhile, the article also discusses the current key challenges in MAAs biosynthesis research, including low precursor content, insufficient enzyme catalytic activity, and difficulties in accurate product identification, which collectively hinder the industrial development of MAAs. Breaking through these technical bottlenecks is expected to enable the development of sustainable and economically viable approaches for the large-scale production of MAAs. This review introduces the current status of research on MAAs synthesized by microbial cells from multiple perspectives and makes a prospective analysis of future development trends, aiming to provide a reference and guidance for research on microbial synthesis of MAAs. Biosynthesis technology shows promise in replacing traditional extraction methods, potentially revolutionizing the production mode of MAAs fundamentally. This innovative production approach will not only satisfy the growing demand for MAAs in the cosmetics industry, but will also significantly improve the accessibility and usage of MAAs in multiple fields.

Lactic acid bacteria (LABs) are a group of Gram-positive bacteria that metabolize soluble carbohydrates to produce lactate as the main metabolite. Certain LABs have a long history of use in fermented foods and are generally considered as safe. On the other hand, LABs are commensal bacteria of the human body and have been shown to exert beneficial effect on the host, such as regulating the balance of intestinal and skin microecology and enhancing the body's immunity. At present, the addition of LABs and their active metabolites to skin care products could enhance moisturizing, antioxidant, and allergy-reduction effect, which have been accepted by consumers. The roles of LABs in treating skin diseases are also supported by more and more experimental data. With the rapid development of genetic tools, LABs have been explored to effectively produce value-added food and biomedical products such as organic acids, alcohols, and exopolysaccharides. Moreover, recent advances in synthetic biology have been used to engineer LABs for delivering therapeutic molecules in response to disease signals, showing attractive application prospect for disease therapy insitu. In the field of skincare, LABs are an attractive chassis for being engineered to produce bioactive substances for skincare and also as biotherapy carriers for wound treatment, as the food-safe status of LABs. In this review, we summarize the genetic operation systems established for LABs, from genetic accessibility to gene expression systems, and highlight the emerging genome editing techniques for manipulating their genomes. In addition, we comment research progress in producing moisturizing factors and antioxidants using LABs as cell factories. Finally, we expect the feasibility of targeted drug delivery by engineered LABs for healing skin wound and the prevention of infection by pathogenic bacteria, aiming at providing a reference for applying LABs in skin health.

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.

Monoterpenoids constitute a significant subclass of terpenoids, known for their volatility and strong aromatic properties. These compounds are extensively employed across multiple sectors, including pharmaceuticals, foods, flavors, cosmetics, agriculture, and energy, due to their diverse pharmacological and biological activities. Currently, monoterpenoids are primarily sourced from plant extracts or chemical synthesis. However, low yield and high cost associated with plant extracts as well as low purity and high energy consumption with chemical synthesis cannot address the growing demand. As a result, the heterologous synthesis of monoterpenoids using microorganisms presents an alternative pathway that is efficient, sustainable, and eco-friendly. Yeasts show promise as hosts for monoterpenoid biosynthesis due to their fast growth, inherent mevalonate (MVA) pathway, and robust post-translational modification systems. Currently, the industrial production of the artemisinin precursor artemisinic acid and the sesquiterpene farnesene has been achieved using Saccharomyces cerevisiae. Advances in synthetic biology have enabled the construction of microbial cell factories for monoterpenoid synthesis. However, challenges remain in scaling up production due to limited precursor availability and monoterpene cytotoxicity. This review first introduces the foundational pathways of monoterpenoid biosynthesis in yeast, followed by discussion on engineering strategies and advancements in yeast-mediated monoterpenoid synthesis, which include enhancing the supply and utilization of acetyl coenzyme A and geranyl pyrophosphate (GPP), regulating and modifying key enzymes such as GPP synthase and monoterpene synthase, optimizing subcellular organelle localization and compartmentalization of MVA pathway genes and monoterpenoid synthases, and implementing exocytosis and tolerance engineering to mitigate monoterpene cytotoxicity. Future directions and strategies to overcome bottlenecks in microbial synthesis are explored to guide research in yeast synthesis of monoterpenoids.

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.

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.

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.