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.

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.

Ceramide, a fundamental bioactive molecule found ubiquitously in eukaryotic organisms, exerts profound regulatory effect on cellular physiology, encompassing critical roles in signaling cascades, cellular proliferation, differentiation, and apoptosis, as well as immunomodulation. In dermatology, ceramides play an indispensable role as constituents of the stratum corneum, the outermost layer of the skin, where they are crucial for maintaining the integrity of the epidermal barrier, regulating moisture retention, combating oxidative stress linked to aging, and exhibiting notable antimicrobial and anti-inflammatory properties. The multifaceted biological functions of ceramides underscore their extensive applications in various industries, including cosmetics, biomedicine, functional food, and animal nutrition, highlighting their significant market potential and therapeutic value. The chemical synthesis of ceramides poses substantial challenges due to the intricate stereochemistry involved, necessitating precise control over synthetic pathways. As a result, current commercial sources predominantly rely on semi-synthetic methods that integrate traditional natural extraction techniques with biochemical transformations of sphingolipid precursors to achieve targeted ceramide structures. Recent advancements in synthetic biology have explored microbial systems for the production of sphingolipids, including ceramides, offering promising avenues for scalable and sustainable synthesis. However, optimizing de novo synthesis pathways and their efficiency in microbial cell factories remains a primary research focus. Strategies aimed at enhancing ceramide yield and purity through metabolic engineering and pathway optimization are pivotal for advancing industrial applications. This paper provides a systematic review of the physiological effectiveness and function of ceramides, encompassing their physiological roles and various applications. It begins with an overview of ceramide extraction methods, including both natural extraction techniques and chemical synthesis approaches for ceramides and their precursor compounds. Subsequently, the review addresses the sphingolipid synthesis pathways and their associated key enzymes, detailing strategies for pathway regulation and optimization, as well as the aspects of product transport, storage, and secretion. Additionally, it explores the identification and expression of key enzymes. The paper concludes by examining future directions in the field, such as addressing aggregation toxicity in ceramide synthesis, enhancing transport and secretion mechanisms, advancing digital modifications of catalytic elements, and expanding gene regulatory target exploration. By synthesizing current knowledge and highlighting avenues for innovation, this review aims to catalyze further research effort toward achieving efficient ceramide production. Ultimately, optimizing ceramide synthesis has the potential to unlock its full potential in various sectors, contributing to its advancement in skincare, therapeutics, and functional materials. The integration of microbial systems is particularly promising for expanding production capabilities while addressing sustainability concerns in ceramide manufacturing. Continued advancements in synthetic biology and biotechnology are expected to revolutionize the landscape of ceramide applications, paving the way for enhanced therapeutic interventions and novel industrial applications in the future.

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.

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.

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 field of synthetic biology has been profoundly transformed over the past two decades due to major advances in biotechnology. Notable instances of this seismic shift can be seen in DNA sequencing, where the cost for human whole genome sequencing (WGS) has dropped by ten million-fold in the past 20 years from nearly 3 billion USD in 2003 to less than 300 USD currently. For perspective, in the field of computer technology the effects of “Moore’s Law” has drove computation cost down by a thousand-fold in the past 20 years. Significant advances in technologies underpinning synthetic biology in recent years are transforming many major industries, and one remarkable example of synthetic biology driven transformation is the cosmetics and skincare industry. Historically, changes in skincare have been driven by changes in raw materials: from ancient plant-based concoctions to industrial-era chemicals in the twentieth century, and later to the concept of “cosmeceuticals” emerged in the U.S., integrating pharmaceutical benefits into cosmetics to meet the growing demand for anti-aging skincare products. Today, there’s an increasing demand for more potent cosmetics, alongside a growing voice for environmentally sustainable production. Traditional skincare product development often involves reformulating existing ingredients, which faces limitations in efficacy. Additionally, the reliance on chemical synthesis or natural extraction methods for production poses additional environmental cost due to the use of chemical reagents and significant energy consumption. Rapid advances in biotechnology enables us to overcome such efficacy and environmental limitations through direct synthesis of biomaterials that are safer and more cost-effective than their industrial chemical counterparts. Synthetic biology tools such as AI-assisted protein design and strain engineering are enabling the production of much more potent biomaterials at industrial scales, thus providing more effective and sustainable bioactive ingredients for skincare. For example, previously expensive and hard-to-obtain compounds such as hyaluronic acid, ceramides, and collagen are now produced at a fraction of the cost compared to the previous decade. In recent years, synthesized collagen has shown that it can be designed to be humanized to minimize adverse human immune reactions, thus greatly reducing allergy and other health risks of the end product. The incorporation of biomaterials that were once exclusive to expensive therapeutics into consumer skincare product is rapidly transforming the cosmetics industry by narrowing the gap between medical-grade treatment and consumer-grade anti-aging. This trend marks a significant leap toward more effective, safer, and environmentally sustainable cosmetics products. Ultimately, the advent of synthetic biology-based cosmetics is ushering in the transitioning from traditional industrial chemical-based cosmetics to a new era of “bio-cosmetics”.