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  • Jinhang YI, Yulin TANG, Chunyu LI, Heyun WU, Qian MA, Xixian XIE
    Synthetic Biology Journal. 2025, 6(2): 254-289.

    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.

  • Mengyao ZHANG, Peng CAI, Yongjin ZHOU
    Synthetic Biology Journal. 2025, 6(2): 334-356.

    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.

  • Zhouhuang SHENG, Zhixian CHEN, Yan ZHANG
    Synthetic Biology Journal. 2025, 6(2): 408-421.

    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.

  • Qi GAO, Wenhai XIAO
    Synthetic Biology Journal. 2025, 6(2): 357-372.

    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.

  • Hongtao JIAO, Meng QI, Bin SHAO, Jinsong JIANG
    Synthetic Biology Journal. 2025, 6(1): 177-189.

    DNA data storage is a key for the development and application of synthetic biology. With the advent of high density storage technology for long period and more stable and secure data storage, the shortage of storage capacity caused by the explosive growth of data can be addressed. Thus, exploring the legal issues for the storage of DNA data is more important than ever for ethics with the emerging science and technology. At the human rights level, human dignity and privacy need to be protected, and the data gap between human beings available and unavailable to the data to be minimized, through the development of complete policy and legal systems for DNA data storage. At the security level, it is suggested to strengthen the security governance of DNA data storage technology by combining information security and biosafety issue. At the level of intellectual property, it is suggested to improve patent protection, and optimize the legal environment of intellectual property, so as to promote the technological innovation and application of DNA data storage technology.

  • Shuyuan GUO, Qiannan ZHANG, MAIMAITIREXIATI Gulikezi, Yiqun YANG, Tao YU
    Synthetic Biology Journal. 2025, 6(1): 18-44.

    With the socioeconomic development, the dependence of human beings on fossil fuels has led to their shortage and climate change. This has created an urgent need for alternatives that are renewable and environmentally friendly, and biofuels are one of them. Nowadays, widely recognized biofuels like fuel ethanol and biodiesel face challenges in terms of their production capacity due to limitation on raw materials such as grains and edible oils and high cost as well. Hence, the integration of metabolic engineering and synthetic biology has opened avenues for utilizing diverse substrates from other renewable sources, such as solar energy, light energy, electric energy, and waste biomass. Microbial cell factories, including microalgae, bacteria, and yeast, play a crucial role in synthesizing biofuels. The review comments on the evolution of the four generations of biofuels, encompassing fuel ethanol, biodiesel, bio-gasoline, jet and aviation fuels. We also discuss how microorganisms can be explored for producing the third- and fourth-generation biofuels from a variety of unconventional substrates such as carbon dioxide, methanol, and methane, multi-energy coupling to synthesize biofuels from lignocellulose by bacterial or yeast, CO2 conversion by microalgae or electrochemical-biological systems, the conversion of methanol and methane by methyltrophic microbes, and the application of synthetic biology. Furthermore, we overview biosynthetic pathways and engineering strategies for optimizing biofuels production. These strategies can convert raw materials to various fuel products, including fatty acids and esters, advanced alcohols and esters, isoprenoids, and polyketides. Finally, we highlight some challenges in biofuels production, including raw material supply and cost issue, low production yield, and limited product variety. Meanwhile, to address these challenges, we propose corresponding solutions. For example, by optimizing carbon fixation pathways, and converting carbon dioxide into low-carbon substrates like methanol, autotrophic microorganisms, methylotrophic microorganisms, and other cell factories can utilize carbon dioxide as the major raw material to synthesize various biofuels, which can benefit the application of biofuels and further promote their industrial production.

  • Ying DONG, Mengdan MA, Weiren HUANG
    Synthetic Biology Journal. 2025, 6(1): 105-117.

    The CRISPR-Cas gene editing technology has revolutionized the fields of biology, medicine, agronomy, etc. due to its simplicity and efficiency. Laboratory-developed tools, such as the widely recognized CRISPR-Cas9, have played a pivotal role in addressing a multitude of genetic diseases. By harnessing the targeted nucleic acid capabilities of the CRISPR-Cas system, researchers have successfully integrated various functionalities into Cas proteins, including fluorescent markers, transcriptional regulatory proteins, and base editing components. This has unlocked new possibilities, including chromosome imaging, transcriptional regulation, and precise base editing. Currently, Cas nucleases with large molecular weights, often exceeding 1000 amino acids, are commonly used. However, adeno-associated virus (AAV) vectors, which are extensively employed in gene therapy, have limited capacity to accommodate additional functional components beyond the coding sequences of CRISPR nucleases and guide RNAs (gRNAs). This limitation severely constrains their utilization in gene therapy and other applications. As a result, a significant focus of research has been placed on the miniaturization of CRISPR tools, making them compact enough to align with current delivery methods. Compact Cas protein variants within CRISPR-Cas systems hold the potential to create and deliver genome editing and regulatory tools into human cells using AAV. Hence, the development of miniaturized CRISPR-Cas systems presents a crucial avenue for addressing this technical challenge. This article provides a comprehensive review of research progress in miniaturizing key proteins within two classes of Cas systems: Cas9 and Cas12 for targeting DNA, and Cas13 for targeting RNA. This review encompasses the screening of novel Cas proteins, the reduction of protein structural domains, and the modification of guide RNAs, all with the intention of presenting innovative ideas for the further advancement of compact, precise gene editing, and regulatory tools. The miniaturization of CRISPR-Cas systems is a critical step toward unlocking their full potential in various fields, including biomedicine, agriculture, and basic research. As researchers continue to explore and refine these compact gene editing and regulatory tools, we can expect significant advancement in understanding and manipulating genetic information. This ongoing progress promises to have a profound impact on the future of science and technology. At present, the limitations of the miniaturized CRISPR-Cas system are mainly with the size of protein molecular weight and the efficiency and specificity of gene editing. If we can solve these problems and obtain a smaller structure in future research, not only can we optimize the transmission of the system in the body, but also develop high-efficiency and low-damage treatment methods for clinic applications.

  • Xiaoyue LIU, Pandi WANG, Gang WU, Fang LIU
    Synthetic Biology Journal. 2025, 6(1): 136-156.

    Glucoraphanin (GRA), a secondary metabolite of plants, is a glucosinolate (GSL) derived from methionine. It is relatively stable in nature, and both GRA and its degradation product sulforaphane (SFN) play important roles in anticancer, neuroprotection, and other broad biological functions and health-benefits, and in particular, SFN has been reported as the best natural product for anticancer. In this article, we review the physicochemical properties, sources, biological functions, synthetic pathways, current production status of GRA, and discuss the potential strategy for the efficient biological synthesis of GRA in the future. The synthesis pathway of GRA involves three stages: side chain elongation, core structure information, and side chain modification. GRA can be converted into SFN and other active compounds by plant myrosinase (MYR) and intestinal microorganisms. Brassicaceae crops such as broccoli have high levels of GRA, and are currently the main source of GRA. However, the cultivation cycle of GRA-rich plants is long, and its extraction yield is low. Therefore, the development of economical and renewable new resources of GRA will greatly advance its applications. With the elucidation of the biosynthesis and regulation pathways of GRA, its genetic engineering-assisted efficient biological synthesis shows great potential, suggesting that the possibility for developing strategies with the manipulation of multiple genes for regulated expression at different dimensions to synthesize GRA more efficiently compared to the current mainstream strategy through manipulating single genes. This review focuses on the genetic engineering-assisted efficient biosynthesis of GRA in Brassicaceae crops, systematically outlining potential genes for engineering at each stage of GRA synthesis and highlights chassis crop species from the perspective of enrichment organs, aiming to providing ideas and strategies for the future regulation of GRA biosynthesis in plants through transgenic technology and molecular breeding for large-scale sustainable production of GRA.

  • Xinghua TANG, Qianneng LU, Yilin HU
    Synthetic Biology Journal. 2025, 6(1): 203-212.

    Synthetic biology, as a science transforming life science in the 21st century, is interdisciplinary in nature, breaking boundaries, emphasizing human roles, and shaping our way of living through technology, presenting common challenges in the Anthropocene era we live in. As a technology of the Anthropocene, synthetic biology blurs the line between nature and artificiality, merging the two and demonstrating the profound impact of technology on life itself. Synthetic life not only obscures the boundary between nature and artificiality but also transcends traditional disciplinary divisions, becoming a research object across various fields, thereby promoting interdisciplinary collaboration and integration. In this process, the openness of synthetic life and the generative nature of synthetic biology determine its future-oriented characteristics, altering the direction of technological research in the Anthropocene. Finally, the “big questions” and “small questions” that the philosophy of technology concerns about are unified in synthetic biology. Synthetic biology encompasses both general issues and its specific developments and applications. In summary, philosophical reflections on synthetic biology as a technological platform in the Anthropocene contribute to a deeper understanding of synthetic biology within a new theoretical framework.

  • Hanjie YING, Dong LIU, Zhenyu WANG, Tao SHEN, Wei ZHUANG, Chenjie ZHU
    Synthetic Biology Journal. 2025, 6(1): 1-7.

    Non-renewable resources, such as petrochemicals, have made great contributions to modern civilization. However, the extensive use of fossil fuels, which have been buried for hundreds of millions of years, has led to a substantial increase in carbon imbalance. The imbalance leads to severe ecological and environmental problems. Industrial biomanufacturing, often referred to as a “sunshine economy”, represents a novel sustainable production paradigm, utilizing renewable resources in a carbon-cycling mode. This paper discusses several ways in which biomanufacturing can support China’s “carbon peaking and carbon neutrality” goals from the perspectives of manufacturing feedstock, production mode and product usage. Biomanufacturing can reduce carbon emissions through feedstock substitution, technology iteration and product replacement. Utilization of straw biomass, producing non-food proteins and establishing a biobased industry landscape are important approaches for reducing carbon emissions in biomanufacturing. Efficient biomanufacturing of food and natural products can substantially improve production efficiency, conserve significant land resources, and thus provide land resources for “carbon replacement”. Optimizing agricultural products through biotechnology advancements and innovative product development is a crucial way to reduce pollution but also enhance the carbon sink capacity of the agricultural sector.