Arbutins are a kind of natural glycoside compounds found widely in nature. α-arbutin, one of its isomers, has received increasing market attention due to its efficient and safe whitening effect and other excellent pharmacological effects. Studies have revealed that the production methods of α-arbutin mainly fall into three categories: plant extraction, chemical synthesis, and biosynthesis. For the plant extraction, raw materials are widely available, and the process is simple, but the yield fails to meet the requirement for large scale production and applications. The chemical synthesis has a higher yield but with harsh reaction conditions, and thus is not environmentally friendly. Through research has found that the biosynthesis of α-arbutin has higher yield, safer environment, more competitive cost and other advantages compared with the natural extraction and chemical synthesis as well, making it the mainstream production method. This article discusses the advantages and disadvantages of different synthetic methods and studies on the seven enzymes commonly used in the biosynthesis of α-arbutin including α-amylase, sucrose phosphorylase, cyclodextrin glycosyltransferase, α-glucosylase, dextransucrase, amylosucrase, and sucrose isomerase. These enzymes use different sugar donors and catalyze the transglycosylation reaction with hydroquinone as the receptor substrate to synthesize α-arbutin. Additionally, we provide a comprehensive review on research progress in the whole-cell catalysis and microbial fermentation to produce α-arbutin, and potentials for its industrial production are assessed. Furthermore, we highlight challenges that exist in the biosynthesis of α-arbutin, such as the oxidation of hydroquinone during synthesis that increases cell toxicity and reduces the yield, the low utilization rate of glucose and the generation of other glycoside products, and the poor performance of experimental strains, and corresponding solutions are proposed. Finally, future directions for α-arbutin synthesis are prospected, with the aim of providing new ideas for achieving more efficient and lower-cost production of α-arbutin and enhancing its applications in the fields of cosmetics and medicines.

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.

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.

Protein engineering performs specific designs and modifications on proteins through directed evolution, semi-rational or rational design, computer-assisted design, and so on. The engineered proteins, with improved properties, have significant applications in food, medicine, fuel, and material industries. For the chemical and pharmaceutical industry, engineered enzymes can serve as efficient biocatalysts for the synthesis of active pharmaceutical ingredients (API) and their intermediates, aligning with the concepts and principles of green chemistry and manufacturing. For the biopharmaceutical industry, the engineering of peptide or protein modifying enzymes can boost the efficiency in preparing drug candidates, while engineered diagnostic enzymes can make detection more accurate and sensitive. Moreover, protein engineering can improve the bioactivities of biological drugs such as therapeutic enzymes and antibodies, increase stability, and mitigate immunogenic response for their safety and efficacy. Here, we review the tremendous progress in protein engineering, elucidate its importance in the research and development of chemically derived drugs and biologics, and provide examples of its applications. These examples encompass the discovery of enzymes or antibodies, the process of protein engineering, and the subsequent economic advantages. We aim to showcase the practical implementation of protein engineering in the pharmaceutical industry and facilitate technology transfer, thereby fostering seamless integration between research, development, and industrial production. Furthermore, we discuss challenges such as cost-effectiveness and market changes in the synthesis of API, and multi-target optimization, long cycle and high risk in the discovery and development of biopharmaceuticals. Finally, we look forward to the prospects of protein engineering in pharmaceutical industry. In the future, automated pipelines consisting artificial intelligence and self-driving laboratories will accelerate the design-build-test-learn cycle, leading to rapid progress in molecular design and discovery.

Optogenetics represents an advanced technology that facilitates precise control of gene expression and neuronal activity in living cells through light. Introduced by neuroscientist K. Deisseroth in 2005, this methodology has transformed neuroscience research, empowering researchers to modulate excitable tissues and neural circuits with exceptional spatiotemporal accuracy. Optogenetics necessitates the expression of light-sensitive proteins, including channelrhodopsins, halorhodopsins, and various microbial opsins, within specific cells. Employing viral vectors and tissue-specific promoters, these proteins ensure targeted expression. Exposure to designated wavelengths of light permits these proteins to activate or inhibit cellular activity, thereby modulating neuronal behavior. The implementation of optogenetics has significantly enhanced comprehension of learning, memory, and neural plasticity. This technology enables the examination of the molecular dynamics associated with synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), which are pivotal for memory. Real-time manipulating of specific neuronal populations can elucidate the intricate neural circuits involved in these phenomena. Additionally, optogenetics has facilitated the exploration of potential therapeutic approaches for neurological conditions such as Alzheimer’s disease by meticulously controlling memory-associated circuits. The utility of optogenetics transcends fundamental research, yielding promising prospects in addiction to studies and motor function enhancement. By modulating distinct neural circuits, it is possible to alter addiction-related behaviors and augment motor functions. Furthermore, the amalgamation of optogenetics with cutting-edge technologies like artificial intelligence and deep learning is anticipated to refine stimulation protocols, resulting in more precise and efficacious experimental outcomes. Notwithstanding its transformative capacity, the clinical application of optogenetics encounters significant obstacles, including the requisites for safe and effective gene delivery systems and the formulation of light-sensitive proteins with optimal characteristics for applications in human beings. Future investigations should concentrate on surmounting these hurdles while expanding the applications of optogenetics in neuroscience and related fields. The integration of optogenetics with multidisciplinary approaches is poised to unveil new realms in brain research, yielding profound insights into mechanisms governing memory, learning, and neural plasticity.

During gene transcription, RNA polymerase initiates the process by recognizing the promoter sequence, and terminates it upon recognizing the terminator sequence located at the 3′-UTR, leading to dissociation of the transcription complex. Therefore, promoters and terminators within the transcription unit play the role of initiating and terminating transcription, respectively. For downstream transcription units, in addition to the direct effect of terminating transcript read-through, the dissociation of the RNA polymerase from the terminator may affect the binding of the promoter to RNA polymerase in the subsequent transcription unit, thus indirectly altering the expression of the downstream transcription unit. This interplay between terminators and promoters across transcription units remains poorly understood, therefore, elucidating the impact of terminators on the transcriptional strength of downstream transcription units is of great significance for the precise regulation of gene expression and the development of efficient terminators. In this study, a library containing 405 different combinatorial elements (terminator-spacer-promoter) was constructed by combining nine terminators, five spacer sequences, and nine promoters using one-pot assembly technology. All combinations in the library were sequenced and analyzed in terms of fluorescence intensity based on the FlowSeq technology to establish the correlations between combinatorial sequences and downstream gene expression. The results showed that combinations of weak terminators, short spacers, and strong terminators were more favorable to enhance the expression of downstream genes, while combinations of strong terminators, long spacers, and weak terminators reduced the expression of downstream genes. Quantitative analysis of transcription revealed that weak terminators not only enhanced downstream leakage transcription (21~70-fold enhancement), but also facilitated downstream promoters to re-recruit RNA polymerase for re-promoted transcription (2~3-fold enhancement). This study has elucidated the effect and mechanism of terminators on the regulation of gene expression in the downstream transcription units, providing a design framework for the construction of gene circuits using terminators.

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.

DNA information storage is a new technology that uses DNA molecules as data carriers. It encodes information for synthesizing DNA with a specific sequence and reads out data through sequencing technology. Compared with traditional magnetic, optical, and electronic storage media, DNA storage has significant advantages in data density, retention duration, energy efficiency, and security, since it is not easily affected by electromagnetic interference. With the rapid increase in the total amount of global data, DNA storage has gradually become a research hotspot with its efficient storage capacity, low maintenance cost, and unique chemical property for synthesizing easily. However, DNA storage technology is still in its early stages of development and there are still many technical bottlenecks to be addressed. For example, an important advantage of DNA storage is its ultra-high storage density and long-term stability. However, achieving these goals require overcoming many technical challenges, such as reducing the error rate for synthesis and improving the encoding efficiency. Understanding existing key technologies, such as DNA encoding, error correction, random access, and DNA information encryption, can help identify and address those shortcomings, thereby promoting further technological innovation and development in DNA storage. Encoding strategy is one of the core aspects of DNA storage technology, directly determining data storage efficiency, reading accuracy, and error correction capability. To achieve efficient and stable DNA information storage, it is essential to develop more advanced encoding algorithms to enhance storage density, reduce synthesis and sequencing error rates, and ensure data accuracy and integrity. Moreover, the information security of DNA storage is becoming increasingly important, particularly in terms of data and privacy protection. As a potential data carrier, DNA storage needs to address challenges related to data encryption, information security, and tamper-proof to ensure data confidentiality and integrity. Therefore, integrating modern cryptographic techniques with DNA storage to establish a secure and reliable information storage system has become a key research focus in this field. This article first introduces the basic process of DNA storage, and then reviews the key technologies involved in DNA information storage, especially the research progress of encoding strategies, error correction technology, random access and DNA information encryption. In addition, the current development status and main challenges of DNA storage technology are also discussed. For example, the scale of DNA data storage in the laboratory is small, and the operation time for synthesis is long. Moreover, most DNA storage steps rely on experimenters, making it difficult to automate the information storage and reading process. With the advancement of synthetic biology and encoding and decoding methods, we believe that these bottlenecks will be solved in the near future, and promote the transformation of technology from laboratory research to practical applications.

Biomanufacturing is a green production that applies such bio-organisms as plants, animals, microorganisms, enzymes as well as in vitro synthetic enzymatic biosystems, to process and/or synthesize numerous value-added compounds, which would change the world′s future of industrial manufacturing in the energy, agricultural, chemical, and pharmaceutical industries. The competition of biomanufacturing is a key part of the battlefield of science and technology. Here we attempt to apply the ancient Chinese philosophy to provide enlightenment to the future development of industrial biomanufacturing. The ancient Chinese philosophy of “Tao-Fa-Shu-Qi” encompasses four key elements: “Tao is a way or direction, Fa is rules, Shu is techniques, and Qi is tools for accomplishing goals”. First, we define and explain the “Tao and Fa” of industrial biomanufacturing analyzes. Second, we analyze the limits and restriction set by Fa. Third, we expound this philosophy of “Tao and Fa” and how it guides way or choice of biomanufacturing type for the desired products. Based on “Tao-Fa-Shu-Qi”, we also present some predictions that a few hot products cannot be manufactured economically by seemingly-promising new techniques based on the limits and restriction of Fa. We take Amyris, a pioneering American company in synthetic biology as an example to analyze and discuss the important roles of “Tao and Fa” in the selection of biomanufactured products, far more important than “Shu and Qi”. Amyris’ failure was destined at its beginning because it went a wrong way (Tao) and ignored basic laws (Fa), although it exhibited advanced abilities of technologies and tools (“Shu and Qi”). Also, we briefly discuss opportunities and challenges of ensuring food security of China by using two disruptive technologies-making synthetic starch from lignocellulosic biomass and carbon dioxide catalyzed by in vitro synthetic enzymatic biosystems. In a word, the ancient Chinese philosophy “the way is simple, from top to down, the way guides techniques and tools” would provide top-level design methodology, identify the future research and development priorities in industrial biomanufacturing, and help effectively solve the major challenges, such as food security, dual carbon goals, and sustainable development.

As a class of enzymes widely distributed in nature, peroxidases are involved in important life processes such as innate immunity and epidemic prevention of organisms, anti-oxidative stress of plant microorganisms, fungal lignin degradation, plant cell wall metabolism and wound healing. With the rapid development of DNA sequencing, gene editing, recombinant protein expression and high-throughput screening technologies, more and more peroxidases have been discovered, characterized and recombinantly expressed. These peroxidases, characterized by their species diversity, abundant quantity, and excellent catalytic performance, have attracted extensive attention in many fields of application research. In recent years, remarkable progress has been made in the recombinant expression of peroxidases, further promoting their development in the field of applied research. Additionally, as we deepen our understanding of the catalytic properties of peroxidases, new opportunities have emerged for their application in the field of biosynthesis. Their high catalytic activity allows for rapid oxidation reactions under mild conditions and enables the construction of multi-enzyme cascade systems in conjunction with other enzymes, thereby facilitating the efficient synthesis of complex compounds. This paper provides a brief overview of peroxidases from the perspective of systematic evolutionary classification and function. It systematically reviews recent progress in the recombinant expression of peroxidases in Escherichia coli, yeast, and fungi, as well as their application achievements in environmental remediation and compound detection. The focus is on the latest research advances in the application of peroxidases for the biosynthesis of high-value-added compounds. The paper also discusses the current issues in this field, such as substrate and product non-specificity and the cytotoxicity of the cofactor H₂O₂. Peroxidases have enormous potential for applications in medical diagnostics, environmental protection, and biosynthesis. However, current technologies and applications still face several challenges, such as the stability and activity of peroxidases in complex environments, high production costs of enzyme preparations, and poor specificity. In the future, by integrating the latest advances in protein engineering, synthetic biology, and immobilization technology, these challenges can be effectively solved, promoting the widespread application of peroxidases across various fields.