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Synthetic biology drives the sustainable production of terpenoid fragrances and flavors ZHANG Mengyao, CAI Peng, ZHOU Yongjin Synthetic Biology Journal    2025, 6 (2): 334-356.   DOI: 10.12211/2096-8280.2024-057 Abstract （3015）   HTML （207）    PDF（pc） （3063KB）（2119）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Synthetic biology ushers cosmetic industry into the “bio-cosmetics” era ZHANG Lu’ou, XU Li, HU Xiaoxu, YANG Ying Synthetic Biology Journal    2025, 6 (2): 479-491.   DOI: 10.12211/2096-8280.2024-056 Abstract （2581）   HTML （196）    PDF（pc） （1267KB）（2805）       Knowledge map    Save 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”. Table and Figures | Reference | Related Articles | Metrics

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Research progress in the biosynthesis of salidroside HUANG Shuhan, MA He, LUO Yunzi Synthetic Biology Journal    2025, 6 (2): 391-407.   DOI: 10.12211/2096-8280.2024-076 Abstract （2013）   HTML （149）    PDF（pc） （1809KB）（3176）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Advances in biosynthesis of L-arginine using engineered microorganisms WANG Qian, GUO Shiting, XIN Bo, ZHONG Cheng, WANG Yu Synthetic Biology Journal    2025, 6 (2): 290-305.   DOI: 10.12211/2096-8280.2024-068 Abstract （2000）   HTML （118）    PDF（pc） （1555KB）（2141）       Knowledge map    Save 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 Corynebacteriumglutamicum and Escherichiacoli 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. Table and Figures | Reference | Related Articles | Metrics

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Advances in small-molecule biopesticides and their biosynthesis SONG Kainan, ZHANG Liwen, WANG Chao, TIAN Pingfang, LI Guangyue, PAN Guohui, XU Yuquan Synthetic Biology Journal    2025, 6 (5): 1203-1223.   DOI: 10.12211/2096-8280.2024-078 Abstract （1906）   HTML （118）    PDF（pc） （3268KB）（1572）       Knowledge map    Save Small-molecule biopesticides, in contrast to chemically synthesized pesticides, demonstrate superior degradability in the natural environment and exert a lesser adverse impact on non-target organisms and the overall ecosystem. Consequently, the evolution of small-molecule biopesticides represents a pivotal shift for the pesticide industry towards more sustainable and environmentally benign practices, with their significance projected to escalate in the realm of agricultural production in the years ahead. Despite their potential, these pesticides are currently constrained by a limited variety and suboptimal production yields, primarily attributable to the intricate research and manufacturing processes that demand substantial time and resource investments. Moreover, the biosynthetic pathways of the majority of these small molecules remain enigmatic, posing a significant challenge to their industrial application. However, the advent of synthetic biology and metabolic engineering offers promising solutions to these impediments. This progress is not merely instrumental in deepening our understanding of the intricate synthetic mechanisms of these bioactive compounds within biological systems, but it also paves the way for augmenting their production yields. By employing microbial cell factories, these technologies enable an efficient and targeted biosynthesis of specific biopesticides, thereby overcoming the limitations associated with traditional extraction and purification methods from natural sources. Microbial cell factories not only facilitate the cost-effective and environmentally friendly large-scale production of small-molecule biopesticides but also foster the innovation of novel biopesticide varieties. This review aims to summarize the small-molecule biopesticides and some semi-synthetic pesticides derived from natural products that were registered in China from January 2000 to December 2024, including eight polyketides, twelve terpenes, four alkaloids, and five other small-molecule biopesticides. Depending on their specific uses in agricultural practices, they can be classified into insecticides, microbicide, plant growth regulators, and so on. Furthermore, this review provides a succinct overview of the representative biosynthetic pathways and the corresponding microbial cell factories that are pivotal to the production of these biopesticides. We expect that an in-depth understanding of the biosynthesis of small-molecule biopesticides will pave solid ways for further elucidation of biosynthesis pathways, yield improvement, and the discovery and application of novel biopesticides. Table and Figures | Reference | Related Articles | Metrics

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Applications of machine learning in the reconstruction and curation of genome-scale metabolic models WU Ke, LUO Jiahao, LI Feiran Synthetic Biology Journal    2025, 6 (3): 566-584.   DOI: 10.12211/2096-8280.2024-090 Abstract （1904）   HTML （181）    PDF（pc） （1727KB）（3120）       Knowledge map    Save Since the publication of the first genome-scale metabolic model (GEM) in 1999, GEMs have become an essential tool for analyzing metabolism. The models integrate genes, metabolites, and reactions for combining stoichiometric matrices with constraint-based optimization to systematically describe and simulate metabolic processes in organisms. The development of automated pipelines for reconstructing GEMs has expanded their applicability to organisms from all kingdoms of life. Additionally, GEMs can integrate kinetic parameters, thermodynamic parameters, multi-omics data and multi-cellular processes to reconstruct more accurate models, thereby improving prediction accuracy. However, the reconstruction of GEMs remains heavily dependent on pre-existing knowledge, inherently limiting their scope to currently available information. This dependency restricts our ability to fully unravel the complexity and dynamic nature of metabolism. Recent advances in machine learning have demonstrated extraordinary capabilities for biological tasks such as protein structure prediction, disease identification and GEM reconstruction with functional annotation and large-scale data integration, showcasing its power in identifying patterns and uncovering hidden relationships within biological systems. Machine learning provides a promising pathway to overcome the limitations of GEMs by expanding their applicability to areas previously constrained by data availability and complexity. This review summarizes the traditional reconstruction methods of GEMs and their applications in integrating multi-dimensional data to build multi-constraint and multi-process models. The review also focuses on key applications of machine learning in gene function annotation, pathway analysis, gap-filling prediction in the reconstruction of GEMs. Additionally, the potential of machine learning in predicting kinetic, thermodynamic, and other key biochemical parameters in the reconstruction of multi-constraint and multi-process models is discussed. By combining GEMs with machine learning innovations, researchers can improve model accuracy, enhance scalability, and gain new insights into previously elusive metabolic mechanisms, bridging gaps in metabolic knowledge, and underscoring its importance as a cornerstone for future development in systems biology and biotechnology. Table and Figures | Reference | Related Articles | Metrics

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Biosynthesis of flavonoids and their applications in cosmetics WEI Lingzhen, WANG Jia, SUN Xinxiao, YUAN Qipeng, SHEN Xiaolin Synthetic Biology Journal    2025, 6 (2): 373-390.   DOI: 10.12211/2096-8280.2024-058 Abstract （1851）   HTML （124）    PDF（pc） （1916KB）（2829）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Research advances in biosynthesis of hyaluronic acid with controlled molecular weights XIAO Sen, HU Litao, SHI Zhicheng, WANG Fayin, YU Siting, DU Guocheng, CHEN Jian, KANG Zhen Synthetic Biology Journal    2025, 6 (2): 445-460.   DOI: 10.12211/2096-8280.2024-062 Abstract （1767）   HTML （93）    PDF（pc） （2479KB）（976）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Advances in the biosynthesis of monoterpenes by yeast GAO Qi, XIAO Wenhai Synthetic Biology Journal    2025, 6 (2): 357-372.   DOI: 10.12211/2096-8280.2024-049 Abstract （1748）   HTML （167）    PDF（pc） （1642KB）（1613）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Plant synthetic biology: new opportunities for large-scale culture of plant cells YAN Zhaotao, ZHOU Pengfei, WANG Yangzhong, ZHANG Xin, XIE Wenyan, TIAN Chenfei, WANG Yong Synthetic Biology Journal    2025, 6 (5): 1107-1125.   DOI: 10.12211/2096-8280.2024-095 Abstract （1693）   HTML （87）    PDF（pc） （1622KB）（2543）       Knowledge map    Save Plant Cell Culture (PCC) has emerged as a highly promising chassis for synthetic biology, offering a range of advantages such as short growth cycles, cost-effectiveness, absence of pathogenic risks, and abundant secondary metabolites. These features make PCC an attractive alternative for applications in medicine, food, and health. However, insufficient production efficiency due to difficulties in genetic transformation, complex regulatory networks, cell aggregation, and poor genetic stability remains a major obstacle that limits the commercialization of PCC. Synthetic biology, with its bottom-up engineering design approach, provides a powerful toolkit to address these challenges. By enabling the precise design and modification of native plant cells, synthetic biology offers innovative strategies to develop efficient and economically viable plant cell factories. In this paper, we first review the current status of PCC in synthesizing high-value compounds, particularly recombinant proteins and secondary metabolites. Recent advancements have demonstrated the potential of PCC to produce therapeutic proteins, vaccines, industrial enzymes and bioactive compounds such as alkaloids, flavonoids, and terpenoids. These successes underscore the versatility of PCC as a bioproduction platform. We then explore the role of synthetic biology in advancing PCC industrialization. Key developments include the creation of high-quality plant cell lines through genome editing tools like CRISPR/Cas9, enhancing genetic stability and metabolic efficiency. Additionally, synthetic biology has improved genetic transformation systems, overcoming a critical bottleneck in PCC. Enhanced expression systems, incorporating synthetic promoters and regulatory elements, have significantly boosted target compound yields. Furthermore, synthetic biology has expanded PCC applications by enabling the biosynthesis of heterologous compounds beyond their native metabolic pathways. Finally, we discuss future prospects, emphasizing the potential of synthetic biology to overcome current technical challenges. Emerging technologies including multi-omics integration, machine learning, and synthetic organelle development are anticipated to further enhance PCC’s scalability and efficiency. By addressing these challenges, synthetic biology will pave the way for large-scale plant cell cultivation, thereby facilitating its widespread adoption in industrial bioproduction. The convergence of PCC and synthetic biology holds immense potential for the sustainable, cost-effective, and scalable production of high-value compounds. Table and Figures | Reference | Related Articles | Metrics

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Applications and advances in the research of biosynthesis of amino acid derivatives as key ingredients in cosmetics YI Jinhang, TANG Yulin, LI Chunyu, WU Heyun, MA Qian, XIE Xixian Synthetic Biology Journal    2025, 6 (2): 254-289.   DOI: 10.12211/2096-8280.2024-060 Abstract （1560）   HTML （179）    PDF（pc） （2916KB）（2789）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Plant synthetic biology and bioproduction of human milk oligosaccharides YU Wenwen, LV Xueqin, LI Zhaofeng, LIU Long Synthetic Biology Journal    2025, 6 (5): 992-997.   DOI: 10.12211/2096-8280.2024-089 Abstract （1507）   HTML （87）    PDF（pc） （1105KB）（893）       Knowledge map    Save Human milk oligosaccharides (HMOs) are the third largest solid component in breast milk. They have a wide range of applications due to their beneficial physiological functions such as regulating the immune system, maintaining digestive health, and promoting brain development. There is a growing interest in the development of green and efficient bioproduction of HMOs via synthetic biology technologies. Recently, Patrick M. Shih’s team from the University of California, Berkeley, has engineered the model plant Nicotiana benthamiana as a photosynthetic platform for HMOs production. Specifically, the enzymes involved in HMOs biosynthesis were heterologously expressed in the cytosol to reconstruct the metabolic pathways required for HMOs bioproduction. Furthermore, they optimized the productions of HMOs by enhancing the supply of key precursors. Finally, several HMOs were successfully produced from the cost-effective raw materials CO2. The reported study provides deeper insights into the green bioproduction of HMOs, and expands the potential applications of plant synthetic biology technologies in the green and sustainable bioproduction of other dairy-based functional nutraceuticals. From the perspective of regulatory approval and industrial application, the aforementioned technology remains at the proof-of-concept stage. In contrast, an integrated approach combining CO2 capture and conversion with microbial fermentation shows greater potential for demonstrating scalable green biomanufacturing of HMOs in the near term. Table and Figures | Reference | Related Articles | Metrics

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Biosynthesis and manufacture of microbial oils and vegetable oils SU Juanjuan, ZHENG Jiawen, MIAO Runze, HAN Peng, WANG Shi’an, LI Fuli Synthetic Biology Journal    2025, 6 (5): 1167-1183.   DOI: 10.12211/2096-8280.2024-093 Abstract （1461）   HTML （65）    PDF（pc） （1718KB）（597）       Knowledge map    Save Oils and fatty acid derivatives are essential raw materials across various industries, including food, bioenergy, functional materials, and pharmaceutical chemicals, with significant global demand. Currently, China heavily relies on imported oilseed crops, and the cultivation of oil crops is constrained by limited arable land, making it difficult to meet the growing demand for oils. The development of synthetic biology offers a promising solution, particularly through the microbial oil synthesis technology, which utilizes renewable resources to produce oils, presenting a strategic alternative to traditional oil production methods. The work provides a comprehensive overview of the current research progress in the biosynthesis and biomanufacturing of microbial oils and vegetable oils. It highlights the commercial demonstration cases of microbial synthesis for high-value oils, including arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). It also presents the industrial demonstration cases of bulk oil synthesis, such as biorefining technology that utilizes lignocellulosic materials. The economic differences between vegetable oils and microbial oils are analyzed, emphasizing the challenges and opportunities in cost reduction and scalability. Additionally, the review summarizes the technologies for oil separation, extraction, and detection, which are critical for improving the efficiency and quality of oil production. Looking ahead, high-value oils are expected to undergo rapid development in the short term, driven by their applications in health, nutrition, and specialty chemicals. In the medium to long term, microbial bulk oils hold great potential, especially through the utilization of non-food feedstocks such as lignocellulosic biomass and industrial waste, enabling the transition to a circular economy in the oil industry. The integration of synthetic biology tools, including genetic engineering, metabolic pathway optimization, and high-throughput screening, will be essential for constructing efficient microbial cell factories capable of producing oils with high yields and tailored compositions. Furthermore, the development of low-cost, full-chain biorefining technologies will be crucial for overcoming the economic barriers to large-scale microbial oil production. By addressing these challenges, microbial oils have the potential to revolutionize traditional oil production methods, offering sustainable and environmentally friendly alternatives to meet the increasing global demand for oils. This review underscores the importance of continued research and innovation in synthetic biology and biomanufacturing to unlock the full potential of microbial and plant oils in various industrial applications. Table and Figures | Reference | Related Articles | Metrics

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Research advances in nitrogen fixation synthetic biology LI Chao, ZHANG Huan, YANG Jun, WANG Ertao Synthetic Biology Journal    2025, 6 (5): 1041-1057.   DOI: 10.12211/2096-8280.2025-081 Abstract （1448）   HTML （71）    PDF（pc） （1881KB）（809）       Knowledge map    Save Nitrogen is an essential element for plant growth and development. Legume plants form symbiotic relationships with rhizobia, which facilitates the biological fixation of atmospheric nitrogen (N2) into ammonia (NH3) that is directly usable by the plants through the action of rhizobial nitrogenase. This process reduces the need for chemical nitrogen fertilizers. However, under the pressure of continuously increasing food demand driven by a growing global population, the major non-leguminous food crops for humans, such as maize, rice and wheat, lack the ability to form nodules and establish symbiosis with rhizobia. This results in a heavy dependence on chemical nitrogen fertilizer to maintain high and stable yields. However, the overuse of chemical nitrogen fertilizers has caused serious environmental problems, including soil compaction and acidification, greenhouse gas emissions, and water eutrophication, all of which threaten agricultural sustainability and global food security. To achieve green and sustainable agricultural development and reduce the use of chemical fertilizers, nitrogen-fixing synthetic biology utilizes tools of synthetic biology to modify, optimize, and even de novo design biological nitrogen fixation systems. These engineered systems are applied across agricultural production, environmental protection, and industrial biotechnology, addressing global challenges such as excessive dependence on chemical nitrogen fertilizers, high energy consumption, and environmental pollution. The innovative strategies for bioengineering biological nitrogen fixation in non-leguminous crops can be categorized into the following four aspects. These strategies include engineering rhizobial nitrogen-fixing bacteria to increase nitrogen supply to the host, engineering crops to enhance the ability of plants to recruit nitrogen-fixing microbes in the rhizosphere to improve nitrogen use efficiency, forming nodule-like structures for symbiotic nitrogen fixation, and transferring functional nitrogenase components into plant cells to create self-fertilizing crops. Significant advances have been achieved in all these approaches in recent years, demonstrating their potential to boost yields while reducing fertilizers. This review provides a comprehensive overview of recent breakthroughs in nitrogen-fixing synthetic biology. We also discuss the current challenges and future prospects, offering theoretical insights and technical guidance to support further research and the practical application of biological nitrogen fixation in sustainable agriculture and environmental protection. Table and Figures | Reference | Related Articles | Metrics

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Engineering rhizosphere synthetic microbial communities to enhance crop nutrient use efficiency ZHENG Lei, ZHENG Qiteng, ZHANG Tianjiao, DUAN Kun, ZHANG Ruifu Synthetic Biology Journal    2025, 6 (5): 1058-1071.   DOI: 10.12211/2096-8280.2025-075 Abstract （1439）   HTML （51）    PDF（pc） （1961KB）（1780）       Knowledge map    Save Modern agriculture confronts the dual challenge of suboptimal nutrient use efficiency (NUE) and the escalating chain of environmental burdens. These include increased greenhouse gas emissions, widespread soil degradation, and rising water eutrophication due to excessive fertilizer runoff. In this context, the rhizosphere microbiome, an indispensable symbiotic partner to plants throughout their life cycle, has been shown to critically regulate the transformation, mobilization, and supply of key soil nutrients. This occurs through core ecological mechanisms such as associative nitrogen fixation (e.g., performed by genera including Azospirillum), organic acid secretion-mediated dissolution of insoluble phosphorus (as commonly observed in Pseudomonas), and siderophore-chelated iron mobilization, which enhance nutrient accessibility for plant uptake. Recent breakthroughs in synthetic biology have significantly advanced the engineering of stable and efficient Synthetic Microbial Communities (SynComs), propelling this approach into a burgeoning frontier of agricultural biotechnology. SynComs integrate functionally diverse microbial strains to overcome well-documented limitations of single-strain inoculants, such as inconsistent performance and low resilience under field conditions. These designed communities form more stable and robust functional modules within the rhizosphere, leading to improved nutrient cycling and root system health. Beyond their application as agronomic biofertilizers, SynComs also serve as a powerful toolset for deciphering complex microbe-microbe interactions and elucidating synergistic mechanisms between microorganisms and host plants. Despite the considerable promise of SynComs technology, several critical barriers impede its real-world deployment. These include poor colonization stability of artificially constructed communities, limited environmental adaptability across varying agroecosystems with divergent soil properties and climatic conditions, and an insufficient mechanistic understanding of multi-trophic plant-microbe interactions. Additionally, commercialization faces further challenges due to prohibitive costs linked to large-scale production, formulation, and field application, as well as undefined long-term ecological risks such as potential disruption of native microbial communities or horizontal gene transfer. To realize the full potential of SynComs, coordinated multidisciplinary efforts are essential. Research should focus on engineering adaptively intelligent consortia capable of responding to dynamic environmental conditions, creating field-applicable tools for real-time monitoring and precision regulation, advancing scalable deployment strategies amenable to existing farming systems, and establishing rigorous ecological risk assessment protocols. An in-depth understanding of rhizosphere microbiome functions, coupled with the active development of SynCom technologies, represents a pivotal opportunity to address pressing agricultural nutrient management challenges. Such advances can significantly reduce inputs of synthetic fertilizers while enhancing nutrient use efficiency, ultimately promoting a transition toward resource-efficient and ecologically sustainable agricultural systems. Collectively, these efforts posses theoretical value and substantial industrial potential. Table and Figures | Reference | Related Articles | Metrics

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Enabling technology for the biosynthesis of cosmetic raw materials with Saccharomyces cerevisiae ZUO Yimeng, ZHANG Jiaojiao, LIAN Jiazhang Synthetic Biology Journal    2025, 6 (2): 233-253.   DOI: 10.12211/2096-8280.2024-070 Abstract （1413）   HTML （186）    PDF（pc） （2379KB）（2258）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Advances in synthesis and mining strategies for functional peptides TANG Chuan′gen, WANG Jing, ZHANG Shuo, ZHANG Haoning, KANG Zhen Synthetic Biology Journal    2025, 6 (2): 461-478.   DOI: 10.12211/2096-8280.2024-067 Abstract （1366）   HTML （95）    PDF（pc） （1566KB）（3942）       Knowledge map    Save 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. Table and Figures | Reference | Related Articles | Metrics

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Strategies and prospects of synthetic biology in crop photosynthesis SUN Yang, CHEN Lichao, SHI Yanyun, WANG Ke, LV Dandan, XU Xiumei, ZHANG Lixin Synthetic Biology Journal    2025, 6 (5): 1025-1040.   DOI: 10.12211/2096-8280.2024-094 Abstract （1297）   HTML （46）    PDF（pc） （1476KB）（2440）       Knowledge map    Save Photosynthesis is the primary source of energy and materials for nearly all life activities on Earth, and its efficiency directly impacts crop growth and yield. With the rapid development of synthetic biology, researchers have begun to explore engineering approaches to optimize the fundamental processes of photosynthesis at various levels, including light energy utilization, carbon fixation, photorespiration, and stress adaptation. This review summarizes recent advances in improving photosynthetic efficiency, with a focus on the synthetic biological strategies that can be implemented in crops. To achieve efficient light absorption and electron transport, novel light energy conversion models have been developed, involving the engineering of light-harvesting antennae to minimize energy loss and the development of orthogonal electron transport chains to enhance quantum yield. Multi-level optimization strategies have been developed for carbon assimilation pathways, including directed evolution and activity modification of Rubisco, optimization of key enzymes in the Calvin-Benson-Bassham cycle, and the introduction of CO2 concentrating mechanisms into C3 plants. Furthermore, novel photorespiratory bypasses have been engineered through synthetic biology approaches, which optimize glycolate metabolism to effectively reduce photorespiratory carbon loss while enhancing photosynthetic efficiency in crops. Additionally, various engineering strategies have been developed to optimize photosynthetic performance under adverse conditions, such as the enhancement of non-photochemical quenching components to tolerate high light and the application of stress-responsive elements to adapt to temperature fluctuations. By employing synthetic biology techniques, significant improvements in plant photosynthetic efficiency and stress resistance have been achieved. This has led to enhanced biomass and crop yields, thereby providing new solutions to address global food security challenges. In the future, strategies based on synthetic biology, combined with a deeper understanding of the molecular mechanisms of photosynthesis and emerging technologies like artificial intelligence, will offer more effective methods and pathways for the engineering of photosynthesis, resulting in a substantial enhancement of crop photosynthetic efficiency. Table and Figures | Reference | Related Articles | Metrics

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Halogenases in biocatalysis: advances in mechanism elucidation, directed evolution, and green manufacturing WANG Mingpeng, CHEN Lei, ZHAO Yiran, ZHANG Yimin, ZHENG Qifan, LIU Xinyang, WANG Yixue, WANG Qinhong Synthetic Biology Journal    2025, 6 (4): 728-763.   DOI: 10.12211/2096-8280.2024-091 Abstract （1264）   HTML （141）    PDF（pc） （8444KB）（2380）       Knowledge map    Save Organic halides, which serve as critical structural motifs in pharmaceuticals, agrochemicals, and advanced materials, are typically synthesized using energy-intensive processes that involve toxic reagents and generate hazardous waste. In contrast, halogenases-nature’s biocatalytic tools-catalyze regio- and stereoselective halogenation under environmentally benign conditions, offering a paradigm shift towards sustainable chemistry. This review systematically consolidates recent breakthroughs in halogenase research, emphasizing mechanistic insights, engineering innovations, and scalable industrial applications. Halogenases are mechanistically classified into three major families: flavin-dependent enzymes that mediate electrophilic halogenation throughtransient hypohalous acid intermediates; non-heme iron/α-ketoglutarate-dependent oxygenases that drive radical-based halogenation pathways; and S-adenosylmethionine (SAM)-dependent enzymes that facilitate rare nucleophilic halogenation. Cutting-edge structural biology techniques, enhanced by computational simulations, have elucidated dynamic substrate-enzyme interactions and transient catalytic states, facilitating the rational design of halogenases with tailored reactivity. , The integration of bioinformatics tools with high-throughput screening platforms has concurrently accelerated the discovery of novel halogenases from underexplored microbial niches, revealing unprecedented catalytic diversity. To bridge natural enzymatic capabilities with industrial demands, interdisciplinary strategies are being deployed: Directed evolution optimizes activity and stability under non-native conditions; computational protein design rebuilds substrate-binding pockets for non-canonical substrates; and synthetic biology frameworks reconstruct halogenation pathways in engineered microbial hosts. These efforts collectively expand the biocatalytic toolbox, enabling precise halogenation of complex scaffolds, including aromatic systems, aliphatic chains, and heterocycles. In industrial contexts, enzymatic halogenation is gaining traction for synthesizing high-value compounds, ranging from antibiotic derivatives and antitumor agents to crop protection molecules, while circumventing the traditional reliance on heavy metal catalysts, extreme temperatures, and halogenated solvents. Emerging applications further extend to the functionalization of biomaterials and fine chemicals, underscoring the versatility of halogenases. Future advancements will likely harness machine learning algorithms to decode sequence-activity landscapes and predict multi-enzyme cascades for tandem halogenation-functional group interconversions. Such developments are in line with global sustainability agendas, positioning halogenases as key biocatalysts in the transition towards circular chemical economies. This review highlights the convergence of enzymology, systems biology, and green chemistry in unlocking the full potential of halogenases, paving the way for next-generation biomanufacturing. {L-End} Table and Figures | Reference | Related Articles | Metrics

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Progress and challenges of synthetic biology in agriculture LIU Jie, GAO Yu, MA Yongshuo, SHANG Yi Synthetic Biology Journal    2025, 6 (5): 998-1024.   DOI: 10.12211/2096-8280.2025-065 Abstract （1262）   HTML （94）    PDF（pc） （2403KB）（587）       Knowledge map    Save Synthetic biology is a multidisciplinary field that has revolutionized agriculture by designing and constructing novel life systems. Due to limited arable land resources, it is inevitable that soil will become polluted with heavy metals, and that pesticide and fertilizer residues will accumulate, resulting in low crop photosynthetic efficiency. Traditional agricultural production cannot meet the challenges posed by modern food demands and climate change. Compared to traditional agricultural technologies, synthetic biology presents a promising approach by incorporating advanced technologies into agricultural systems, allowing more efficient and widespread solutions to global agrarian challenges. It represents a strategic high ground for addressing population growth, climate change, and promoting sustainable bioeconomic development. Synthetic biology has the potential to enhance crop photosynthesis, optimize nitrogen fixation mechanisms, improve biological stress tolerance, increase crop yields, and optimize nutritional quality, thereby promoting sustainable agricultural and ecological development. The advancement of biosensor components, gene circuit design, and related technologies can enhance the utilization of free nutrients, such as carbon and nitrogen in crops, while decreasing reliance on fertilizers. Additionally, by integrating microbial chassis-based cell factories, a sustainable system has been developed to convert biomass waste into safe, nutrient-rich fertilizers, enabling efficient waste-to-resource transformation. This article reviews the development history of agricultural synthetic biology and summarizes the latest research progress in synthetic biology technologies widely used in agriculture, including gene editing, metabolic engineering strategies, the development of biosensor components, gene circuit design and artificial intelligence. The core application areas of synthetic biology in agriculture are elaborated upon, including improvement in crop yield and resource utilization, enhancements in stress resistance, optimization in crop nutrition, and refinements in microbial interactions. Finally, the current challenges facing agricultural synthetic biology and its future development trends are discussed. The multidimensional application of synthetic biology in agricultural will facilitate the circular utilization of energy and resources, effectively ensuring food security and promoting the sustainable development of agriculture in the future. Table and Figures | Reference | Related Articles | Metrics