Most Read Articles

    Published in last 1 year |  In last 2 years |  In last 3 years |  All
    Please wait a minute...
    For Selected: Toggle Thumbnails
    Significant research progress in synthetic biology
    Mingzhu DING, Bingzhi LI, Ying WANG, Zexiong XIE, Duo LIU, Yingjin YUAN
    Synthetic Biology Journal    2020, 1 (1): 7-28.   DOI: 10.12211/2096-8280.2020-057
    Abstract5828)   HTML1093)    PDF(pc) (3953KB)(6920)       Save

    As an emerging, interdisciplinary field, synthetic biology has made great advances in many directions due to wide acceptance of its core principles and rapid progress in DNA synthesis. In this paper, recent development in gene circuits, genome design and synthesis, cell factories, and synthetic microbial consortia is reviewed. The complexity of artificial gene circuits that can be designed and constructed is gradually increasing with more refined control. Synthetic genomes are routinely assembled, expanding from prokaryotes (Mycoplasma to Escherichia coli) to eukaryotes (Saccharomyces cerevisiae), and improved capacity in genome design promotes the research of biological evolution. Metabolic pathways of ever-increasing lengths are constructed based on modularization and orthogonality principles to produce molecules of complex structures, and fundamental rewiring of cellular metabolism is performed for enhanced robustness and compatibility. The design and construction of synthetic microbial consortia have been expanded from two-species systems to multi-species systems, so that more sophisticated functions can be achieved. At the end of this paper, new research directions resulted from the interdisciplinary integration of synthetic biology and other disciplines are discussed.

    Table and Figures | Reference | Related Articles | Metrics
    DNA information storage: bridging biological and digital world
    Mingzhe HAN, Weigang CHEN, Lifu SONG, Bingzhi LI, Yingjin YUAN
    Synthetic Biology Journal    2021, 2 (3): 309-322.   DOI: 10.12211/2096-8280.2021-001
    Abstract5570)   HTML532)    PDF(pc) (3021KB)(2962)       Save

    The external preservation of information enables reliable inheritance of human thoughts, playing important roles in the progress of human civilization. Starting from tying knots in ropes to storing data in magnetic and optical media, these technologies have documented and will continue to record the splendid civilization. However, driven by the global digitalization, the global data volume is growing rapidly and challenging the storage capability of existing storage technologies. DNA, as the natural carrier of genetic information, is believed to be a potential candidate to deal with the data storage challenge due to the revealed high density, long-term duration and low maintaining cost features. In this review, we first describe the fundamental principles and technical processes of DNA information storage. The pivotal position of DNA information storage bridging the biological and digital world is also pointed out. Then, according to the different characteristics of data writing and reading, we categorize these technologies into three storage modes, termed as "DNA hard drive", "DNA compact disc" and "DNA tape", by analogy with the popular storage media correspondingly. "DNA hard drive" mode shows the potential in the volume enlargement of the existing information storage system using oligonucleotide pools. "DNA compact disc" mode provides direct in vivo processing on DNA data storage enabling massive data distribution at low cost. "DNA tape" mode provides intracellular information recoding solutions, which may promote the future developments of cellular computing and communication. The up-to-date progress of these three modes is also summarized. We then discuss the main obstacles and potential technical routes towards practical applications of DNA information storage. We envision a cheaper, faster DNA information storage technology, and its appropriate integration with information storage systems in the future. Finally, we conclude that DNA information storage is a cutting-edge interdisciplinary technology and hope this review can bring more focus and research efforts from various fields to DNA information storage.

    Reference | Related Articles | Metrics
    From chemical synthesis to biosynthesis: trends toward total synthesis of natural products
    Faguang ZHANG, Ge QU, Zhoutong SUN, Jun′an MA
    Synthetic Biology Journal    2021, 2 (5): 674-696.   DOI: 10.12211/2096-8280.2021-039
    Abstract4792)   HTML458)    PDF(pc) (6155KB)(3374)       Save

    The complexity and diversity of natural products have made them a rich source for drug and agrochemical discovery. To overcome the supplying limitation of natural resources, tremendous effort has been made by the academic and industrial communities during the past two centuries for the total artificial synthesis of natural products. In this regard, total chemical synthesis has achieved significant progress, and numerous highly complex natural products have been synthesized through different chemical processes. Despite these great achievements in total chemical synthesis, there are still many challenges including expensive chemical reagents, harsh reaction conditions, difficult control on stereoselectivity, long synthetic route, and low product yield. Notably, the development of synthetic biology has allowed more and more natural products to be produced through biological cell factories, which provides a new and complementary strategy for the synthesis of natural products at a large scale. This review critically comments on the representative advances in total chemical synthesis of natural products (Section 1), and then highlight major progress and trends in the biosynthesis of pharmaceutically important natural products (Sections 2 and 3). In Section 2.1, we selected the production of penicillin, erythromycin, and avermectin as examples to analyze the modification and optimization of natural product biosynthetic pathways. The discovery and utilization of secondary metabolites from microorganisms has been a continuous driving force in the field of natural products. Notably, significant progress has been made in the total biosynthesis of natural products from secondary metabolism via the genetic manipulation of microbial cells. In Section 2.2, we selected Vitamin B12 and Tropane alkaloids as examples to demonstrate the use of heterologous expression and biological production for natural product synthesis. In recent years, on the basis of analyzing the structure of natural products in animals, plants, and microorganisms, great advances have emerged in exploring their biochemical reaction mechanisms and synthetic routes. More importantly, expressing and regulating the relative genes in heterologous microbial cells have enabled the complete biosynthesis of many natural products. Furthermore, in Section 3, human insulin, artemisinin, saframycin, azaphilone, kainic acid, and podophyllotoxin were selected as examples to showcase the power of merging chemical and biological processes for the total synthesis of natural products. Although there are still many challenges in the total synthesis of new and complex natural products, biosynthesis will ultimately play a significant role in the construction of natural molecules and their relative analogues. By taking advantage of the merits with organic chemistry, synthetic biology, and artificial intelligence, the development of highly efficient and automatic biosynthesis could be a trend in this field.

    Reference | Related Articles | Metrics
    Recent progress of synthetic biology applications in microbial pharmaceuticals research
    Cong RAO, Xuan YUN, Yi YU, Zixin DENG
    Synthetic Biology Journal    2020, 1 (1): 92-102.   DOI: 10.12211/2096-8280.2020-036
    Abstract3263)   HTML386)    PDF(pc) (1980KB)(3158)       Save

    Microbial natural products are a major source in the innovation of novel pharmaceuticals, including anti-bacterial, anti-tumor, and immunosuppressive agents for clinical use. Currently, the development of microbial drugs is facing significant challenges due to the growing prevalence of multidrug-resistant bacteria, the continuous emergence of new pathogens and viruses, and the increasing difficulties in the discovery of natural products with new scaffolds. Synthetic biology is an emerging interdisciplinary research area leading to great breakthrough in the field of biomedical sciences in the 21st century, which provides new methods and ideas for drug discovery and development. The application of synthetic biology could unlock the potential of natural product mining, design new biosynthetic routes, and generate much more “unnatural” natural products and structural analogs. This review summarizes the technical innovations of synthetic biology in the field of microbial pharmaceuticals, and its applications in the mining, biosynthesis, and new scaffold generation of aminoglycoside antibiotics, nucleotide antibiotics, ribosomally synthesized and posttranslationally modified peptides, terpenoids, and polyketides in the last five years.

    Table and Figures | Reference | Related Articles | Metrics
    Advances of CRISPR gene editing in microbial synthetic biology
    Yang LI, Xiaolin SHEN, Xinxiao SUN, Qipeng YUAN, Yajun YAN, Jia WANG
    Synthetic Biology Journal    2021, 2 (1): 106-120.   DOI: 10.12211/2096-8280.2020-039
    Abstract3169)   HTML324)    PDF(pc) (2241KB)(3444)       Save

    With the increase of global consumption on fossil resources for energy products and chemicals and their consequent impact on environment, construction of microbial cell factories for efficient production of biofuels and bio-based chemicals from renewable sources has gained much attention. Pathway engineering of the hosts, such as over-expression of key genes, disruption of competing pathways and integration of heterologous pathways, plays significant role in fulfilling such a purpose. Successful implementation of these pathway engineering strategies requires efficient and accurate gene editing tools. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) systems are a powerful gene editing strategy that was found in prokaryotic organisms such as archaea and bacteria, which provide adaptive immunity against foreign elements. When host cells are infected by viruses, a small sequence of the viral genome is integrated into the CRISPR locus to immunize the host cells, and this small sequence is transcribed into small RNA guide that directs the cleavage of the viral DNA by the Cas nuclease. Inspired by the natural talent, many modified CRISPR systems have been developed to modify genes and genomes, including knock-in, knock-down, large deletions, indels, replacements and chromosomal rearrangements. In this review, we briefly comment on the technical basis and advances in CRISPR-related genome editing tools applied for constructing microbial cell factories, with a focus on the CRISPR-based tools for metabolic engineering of the model organisms E. coli and S. cerevisiae. Furthermore, we highlight major challenges in developing CRISPR tools for multiplex genome editing and sophisticated expression regulation. Finally, we propose future perspectives on the application of CRISPR-based technologies for constructing microbial ecosystems toward high production of desired chemicals. We intend to provide insights and ideas for developing CRISPR-related genome editing tools to better serve the construction of efficient microbial cell factories.

    Table and Figures | Reference | Related Articles | Metrics
    Microbial promoter engineering strategies in synthetic biology
    Huimin YU, Yukun ZHENG, Yan DU, Miaomiao WANG, Youxiang LIANG
    Synthetic Biology Journal    2021, 2 (4): 598-611.   DOI: 10.12211/2096-8280.2020-092
    Abstract3149)   HTML394)    PDF(pc) (1858KB)(4042)       Save

    Synthetic biology is of vital importance to the green biomanufacturing industry and sustainable development strategies of our country. Promoter is the core-component of synthetic biology, playing a significant role in highly efficient and fine-tuning expression and regulation of target genes at the transcriptional level. Herein we summarized and discussed the key progress and future frontiers of microbial promoter engineering, particularly for prokaryotic microorganisms. Firstly, we introduced the basic DNA sequence characteristics of promoters and the regular mechanism for promoter recognition and transcription-initiation by RNA polymerase sigma factors. Inducible mechanisms for both negative and positive regulation were particularly highlighted with the typical lac operator of Escherichia coli as an example. Then, effective strategies for obtaining improved-promoters were summarized, which were roughly divided into two categories: endogenous promoter mutation and heterologous promoter replacement. For the endogenous promoter mutation, the following strategies, e.g. point mutation toward sigma factor consensus sequence, coupling optimization of -35 and -10 regions with RBS sequence, random mutation or saturation mutagenesis of UP element or spacer sequences accompanying with promoter library construction and high-throughput screening were emphasized. For the heterologous promoter replacement, strategies such as substituting the native promoter into stronger ones from other microorganisms, introducing phage-source chimeric promoters, tuning the constitutive promoter into inducible pattern and integrating positive regulator(s), were mainly discussed. We further sorted out the representative inducers for inducible promoters reported so far, including both chemical molecules and physical signals. Progress in constitutive promoters of non-model and model microbial organisms were simply summarized as well. Next, arising from the breakthrough development of dynamic metabolic regulation and artificial intelligence (AI), we proposed that the innovative research on identification and evolution of new and unique promoters with dynamic-response features and AI de novo design for promoters with novel/superior functions will be the new frontiers of promoter engineering. Finally, we analyzed the challenging scientific issues in the microbial promoter engineering, from the viewpoint of both basic research and large-scale applications; and further discussed the research priority coupling with the vigorous development of synthetic biology.

    Reference | Related Articles | Metrics
    Recent advances in plant synthetic biology
    Bo ZHANG, Yongshuo MA, Yi SHANG, Sanwen HUANG
    Synthetic Biology Journal    2020, 1 (2): 121-140.   DOI: 10.12211/2096-8280.2020-016
    Abstract3084)   HTML265)    PDF(pc) (2509KB)(2934)       Save

    Synthetic biology is a new interdisciplinary field that combines engineering and biology. With an initial focus on microbial systems, it is now increasingly developed for plants. Plant synthetic biology has been applied to design crops for improved yield and nutritional value. It is also possible to transform plants into living factories for producing high-value natural products. In this review, we first summarize the definition of plant synthetic biology and introduce emerging technologies, including DNA synthesis and assembly, genome editing, genetic transformation targeting nucleus and plastid, and chromosome engineering. We then discuss recent applications in biosensor design, yield and nutrition improvement, and natural product and protein biosynthesis. We conclude with the current challenges and future perspective of this field. We envision plant synthetic biology will revolutionize crop breeding.

    Table and Figures | Reference | Related Articles | Metrics
    Advances in synthetic biomanufacturing
    Yuanyuan ZHANG, Yan ZENG, Qinhong WANG
    Synthetic Biology Journal    2021, 2 (2): 145-160.   DOI: 10.12211/2096-8280.2020-052
    Abstract2984)   HTML468)    PDF(pc) (2003KB)(3052)       Save

    Synthetic biomanufacturing is a paradigm for material processing and synthesis via synthetic biology. It is expected to completely transform the traditional production mode for medicines, chemicals, food, energy, materials and agriculture in the future, trigger new industrial revolution, lead to new economic growth and reshape carbon-based civilization. In particular, the COVID-19 global spread that has accelerated the reshaping process of the world's economic and social development. In the foreseeable future, human life and production patterns will undergo profound changes in medicines and healthcare, food and agriculture, energy and materials, etc., during which demands for new technologies will promote evolution in the field of biotechnology, and the biomanufacturing industry in the post COVID-19 era is facing unprecedented opportunities for revitalization and new challenges. According to the analysis of the research report from the Ministry of Economy, Trade and Industry of Japan, engineered biological cells and their combination with information & artificial intelligence technologies will become the main driving force for the "post-fourth industrial revolution".Synthetic biomanufacturing has the characteristics of cleanliness, efficiency and renewableness that can reduce the impact of industrial economy on the ecological environment. Here, in this review, we summarize the progress of synthetic biomanufacturing with respect to bulk fermentation products, fine and pharmaceutical chemicals, renewable chemicals and bio-based polymeric materials, natural products, foods and the utilization of C1 raw materials. The technological progress, status and potential of industrial applications of many important bio-based products via synthetic biomanufacturing are analyzed and discussed. The development of synthetic biomanufacturing shows great potentials for building up the ecological route of industrial economy and addressing current issues of economic sustainability in terms of limited substrate, high cost, and poor viability, and to form whole new industry chain with sustainable growth. In the future, with the development of synthetic biology, and the integration of new technologies such as artificial intelligence and big data, more and more bio-based products can be produced via synthetic biomanufacturing. The formation of bioeconomy can be promoted, and the sustainable development of human society will be better served.

    Reference | Related Articles | Metrics
    Research advances in synthetic microbial communities
    Zepeng QU, Moxian CHEN, Zhaohui CAO, Wenlong ZUO, Ye CHEN, Lei DAI
    Synthetic Biology Journal    2020, 1 (6): 621-634.   DOI: 10.12211/2096-8280.2020-012
    Abstract2954)   HTML326)    PDF(pc) (2491KB)(2595)       Save

    Synthetic microbial communities are an emerging research field at the intersection of synthetic biology and microbiome. A synthetic microbial community is created artificially by co-culturing of multiple species under a well-defined condition. Synthetic communities that retain the key features of their natural counterparts can act as a model system to study the ecology and function of microbial communities in a controlled way. This review covers important topics and research progress in synthetic microbial communities. We start with a summary of ecological factors that shape the structure of microbial communities, including interactions among microbes, host metabolism and immunity and environmental conditions. We then discuss the methods and experimental techniques in design-build-test-learn (DBTL) cycle, used to study synthetic microbial communities. In addition, we review the potential applications of synthetic microbiome in human health, agriculture, industrial production and environmental remediation. Finally, we summarize key scientific questions for future studies of synthetic microbial communities,including how to construct a controllable and stable microbial interaction network, how to characterize and manage the spatial structure of microbial communities, and how to accurately shape the function of microbial communities.

    Table and Figures | Reference | Related Articles | Metrics
    Artificial intelligence-assisted protein engineering
    Jiahao BIAN, Guangyu YANG
    Synthetic Biology Journal    2022, 3 (3): 429-444.   DOI: 10.12211/2096-8280.2021-032
    Abstract2880)   HTML325)    PDF(pc) (2456KB)(2609)       Save

    Protein engineering is one of the important research fields of synthetic biology. However, de novo design of protein functions based on rational design is still challenging, because of the limited understanding on biological fundamentals such as protein folding and the natural evolution mechanism of enzymes. Directed evolution is capable of optimizing protein functions effectively by mimicking the principle of natural evolution in the laboratory without relying on structure and mechanism information. However, directed evolution is highly dependent on high-throughput screening methods, which also limits its applications on proteins which lack high-throughput screening methods. In recent years, artificial intelligence has been developed very rapidly for integrating into multidisciplinary fields. In synthetic biology, artificial intelligence-assisted protein engineering has become an efficient strategy for protein engineering besides rational design and directed evolution, which has shown unique advantages in predicting the structure, function, solubility of proteins and enzymes. Artificial intelligence models can learn the internal properties and relationships from given sequence-function data sets to make predictions on properties for virtual sequences. In this article, we review the application of artificial intelligence-assisted protein engineering. With the basic and process of the strategy introduced, three key points that affect the performance of the predictive model are analyzed: data, molecular descriptors and artificial intelligence algorithms. In order to provide useful tools for researchers who want to take advantage of this strategy, we summarize the main public database, diverse toolkits and web servers of the common molecular descriptors and artificial intelligence algorithms. We also comment on the functions, applications and websites of several artificial intelligence-assisted protein engineering platforms, through which a complete prediction task including protein sequences representation, feature analysis, model construction and output can be completed easily. Finally, we analyze some challenges that need to be solved in the artificial intelligence-assisted protein engineering, such as the lack of high-quality data, deviation in data sets and lacking of the universal models. However, with the development of automated gene annotations, ultra-high-throughput screening technologies and artificial intelligence algorithms, sufficient high-quality data and appropriate algorithms will be developed, which can enhance the performance of artificial intelligence-assisted protein engineering and thus facilitate the development of synthetic biology techniques.

    Table and Figures | Reference | Related Articles | Metrics
    Synthetic biology and food manufacturing
    Yanfeng LIU, Jingwen ZHOU, Long LIU, Jian CHEN
    Synthetic Biology Journal    2020, 1 (1): 84-91.   DOI: 10.12211/2096-8280.2020-005
    Abstract2566)   HTML272)    PDF(pc) (1190KB)(2300)       Save

    As global environmental pollution intensifies, climate continues to change, and population continues to grow, how to ensure safe, nutritious and sustained food supply faces huge challenges. These challenges put forward new requirements for the future food supply and function. Using synthetic biology technologies to create cell factories applicable in the food industry to convert renewable raw materials into important food components, functional food additives and nutritional chemicals is an important way to solve the problems facing the food industry. This article first introduces the importance of synthetic biology to the innovation and breakthroughs in the field of food manufacturing. Secondly, taking artificial food, plant natural products and human milk oligosaccharide, three typical food products from biological manufacturing, as examples, the current tasks and challenges of food synthetic biology are discussed. Finally, the development trends of synthetic biology and food manufacturing in China are summarized and prospected. By strengthening the development and application of food synthetic biology and the related food biotechnologies and being the first to achieve their industrialization, researchers will be able to seize the frontiers of science and technology and industrial highlands globally and benefit mankind.

    Reference | Related Articles | Metrics
    Scalable mining of proteins for biocatalysis via synthetic biology
    Jianzhi ZHANG, Lihao FU, Ting TANG, Songya ZHANG, Jing ZHU, Tuo LI, Zining WANG, Tong SI
    Synthetic Biology Journal    2020, 1 (3): 319-336.   DOI: 10.12211/2096-8280.2020-028
    Abstract2518)   HTML227)    PDF(pc) (2526KB)(2786)       Save

    Biomanufacturing provides a sustainable alternative to traditional petrochemical processes in producing chemicals, drugs, and functional materials. Enzymes are cores for creating catalytic biosystems with diverse functions. Due to the lack of predictive models for enzyme functions, however, rational design is still challenging. On the other hand, next-generation sequencing reveals millions of diverse natural enzymes, of which only a tiny fraction have been experimentally characterized. Synthetic biology applies engineering principles to study, engineer, and create biological systems. Through standardization and modularization, synthetic biology enables large-scale prototyping of enzyme sequences, which not only helps to identify efficient biocatalytic parts, but also accelerates quantitative understanding of sequence-structure-function relationship. Here we review recent advances in scalable mining of enzymes via synthetic biology. We firstly introduce computational tools for functional clustering and prioritization of promising sequences from enormous genome/protein databases, followed by experimental approaches for high-throughput cloning, expression, and characterization of selected candidates. We then discuss the applications of such tools in systematic studies of enzyme (super) families. We conclude with future perspectives in creating integrated synthetic biology foundries to accelerate enzyme mining.

    Reference | Related Articles | Metrics
    Production of sesquiterpenoids α-neoclovene and β-caryophyllene by engineered Saccharomyces cerevisiae
    Xiaodong LI, Chengshuai YANG, Pingping WANG, Xing YAN, Zhihua ZHOU
    Synthetic Biology Journal    2021, 2 (5): 792-803.   DOI: 10.12211/2096-8280.2021-014
    Abstract2471)   HTML323)    PDF(pc) (2407KB)(1416)       Save

    Sesquiterpenoids α-neoclovene and β-caryophyllene are major components in volatile oils from Panax ginseng, which have been demonstrated to play important roles in antibacteria, antitumor and cardiovascular protection. Moreover, they have attracted attentions for potential use as biofuels with high-energy-density. However, the industrial production of α-neoclovene and β-caryophyllene as well as other sesquiterpenoids are mainly relied on extraction from plant materials, which is too costly for applications at a large scale. Currently, this challenge could be addressed by advances in synthetic biology for natural product biosynthesis. Through heterologously assembling and integrating of their biosynthetic pathways into microbial chassis cells, targeted natural compounds from plants could be produced by microbial fermentation in a sustainable, low-cost and large-scale way. In this study, by comparing the production potential of sesquiterpenes between different Saccharomyces cerevisiae strainsand followed by enhancing the endogenous mevalonate pathway, a yeast sesquiterpene chassis strain (SQTBY03) with an increase of 458 times in farnesyl pyrophosphate production was constructed. Then by inserting the codon-optimized sesquiterpene synthase gene ec38-cs from the endophytic fungi Hypoxylon sp. EC38 and the codon-optimized caryophyllene synthase gene QHS1 from Artemisia annua into SQTBY03, respectively, we built yeast cell factories NCVBY01 and CPLBY01 for de novo production of α-neoclovene and β-caryophyllene at their titers of 25.8 mg/L and 250.4 mg/L, respectively, in shake flasks. Furthermore, fed-batch fermentation using NCVBY01 and CPLBY01 resulted in the de novo production of 487.1 mg/L α-neoclovene and 2949.1 mg/L β-caryophyllene from glucose. It is also possible to further chemically catalyze β-caryophyllene to produce α-neoclovene. Our work provides strategies for the sustainable production of α-neoclovene and β-caryophyllene from glucose through microbial fermentation, which would benefit their applications as medicine and other functional products. In addition, our yeast chassis for the sesquiterpene production could offer a platform for the sustainable production of other valuable sesquiterpenoids via synthetic biology approach.

    Reference | Related Articles | Metrics
    Computational protein design: perspectives in methods and applications
    Fan CAO, Yaoxi CHEN, Yangyang MIAO, Lu ZHANG, Haiyan LIU
    Synthetic Biology Journal    2021, 2 (1): 15-32.   DOI: 10.12211/2096-8280.2020-067
    Abstract2465)   HTML239)    PDF(pc) (2838KB)(1715)       Save

    In computational protein design, the amino acid sequence of a protein is rationally chosen through computations so that the resulting molecule is of desired structure and function. Systematic methods for computational protein design have been developed and validated in increasing number of experiments. Exhibiting strong potential for broad applications, computational protein design has been considered as an important enabling technology for Synthetic Biology. Here we briefly review the history of methods for computational design, which are divided into three sections about heuristic design that based on rules, automatic optimization of amino acid sequences, and de novo main chain design respectively. In the next chapter, we introduce the basic approaches and strategies in details. In proteins energy calculation methods, we introduce physical energy terms and statistical energy terms. Based on these energy calculation methods, we introduce sequence and structure design methods including automated optimization of amino acid sequences, de novo design of polypeptide backbones (with fragment assembling method or sequence independent backbone potentials), designing new interfaces for inter-molecule recognition such as protein-ligand interfaces and protein-protein interfaces, and the concept of negative design. Besides the history and detail of computational protein design methods that mentioned above, we also briefly discuss examples of using computational protein design to support application studies, including enhancing protein structural stability and redesign or de novo design of enzymes, vaccines and protein materials that related to interfaces design. These examples not only present current studies using the computational protein design methods, but also enlighten us on more broader applications in the future. Finally, we analyze some problems that need to be solved in the protein computational design method, such as inefficient in design accuracy, difficulty in characterizing polar interactions, and the need to consider the environment of non-aqueous solvents. We also discuss some aspects of possible application in synthetic biology like biological logic gates design and biosensor design, and application prospects in the medical field such as antibodies, vaccine design, etc.

    Reference | Related Articles | Metrics
    Design of biomolecular sequences by artificial intelligence
    Ye WANG, Haochen WANG, Minghao YAN, Guanhua HU, Xiaowo WANG
    Synthetic Biology Journal    2021, 2 (1): 1-14.   DOI: 10.12211/2096-8280.2020-074
    Abstract2391)   HTML273)    PDF(pc) (2159KB)(2353)       Save

    Based on the concept of learning from nature, transforming and transcending nature, the core of synthetic biology is to optimize, reconstruct and recombine genetic elements in order to build synthetic biological systems that meet our needs. Obtaining desirable biological components is the basis for building and controlling synthetic biological systems. Recently, synthetic biomolecules have been widely used in areas such as metabolic engineering and gene therapy. How to search for biomolecular sequences with specific biological functions from the vast sequence library is a challenge for synthetic biology. With the rapid development of artificial intelligence, intelligent algorithms have shown great potentials in mining complex biological characteristics and designing biomolecules. In this review, the applications of deep generative models for the design of different artificial biological sequences are analyzed from the perspective of exploring new drug molecules, nucleic acid fragment sequences and protein sequence spaces under the guidance of complex feature rules discovered by deep learning technology. Furthermore, combined with the application cases in the design of small molecular compounds, nucleic acids and proteins, the directed optimization strategies for designing artificial biomolecules are summarized and analyzed. In order to evaluate the model-designed molecular sequences, this review systematically analyzes the schemes for sequence design evaluation from different perspectives in applications. As an important information writing carrier of synthetic life systems, how the artificial biological sequence interacts with the complex multi-level regulation in the cell is still an important issue to be studied. In the future, the intelligent design of artificial biological sequence needs to consider the characteristics of biological systems with multi-level regulation that is often coupling. Through the design of biological sequences at different levels, different regulation in natural biological systems should be elucidated at different levels properly for an overall intelligent adaptation and optimization of biological sequences and cell chassis environments.

    Reference | Related Articles | Metrics
    Analysis of global patents for the trend of synthetic biology inventions
    Daming CHEN, Guangming ZHOU, Xiao LIU, Yuelei FAN, Yue WANG, Kaiyun MAO, Xuebo ZHANG, Yan XIONG
    Synthetic Biology Journal    2020, 1 (3): 372-384.   DOI: 10.12211/2096-8280.2020-035
    Abstract2387)   HTML261)    PDF(pc) (2356KB)(2523)       Save

    Synthetic biology is an emerging interdisciplinary field which combines the principles of engineering and biology, aiming at the (re-) design, modification and fabrication of new and existing biological systems. The techniques developed by synthetic biology are revolutionizing biotechnology and the pharmaceutical industry. From the perspective of patent analysis, this article reviews the technological history of synthetic biology and its applications. The development of synthetic biology techniques can be divided into four stages. 1) The first stage before 2005, is represented by the application of gene regulatory circuits in the field of metabolic engineering, and large-scale production of artemisinin precursor in E.coli was achieved. 2) During the second stage from 2005 to 2011, basic research on improving engineered natural and artificial cells was developed rapidly, however the number of patent applications did not increase significantly, but new tools and methods continued to accumulate, reflecting the early development characteristics of "engineering biology". 3) In the third stage from 2011 to 2015, with the development of novel genome editing, as well as the incorporation of those fundamentals into synthetic biology tools, patent application was doubled. 4) At the fourth stage since 2015, the design-build-test (DBT) cycle of synthetic biology has been extended to the design-build-test-learn (DBTL) cycle, therefore enabling broader convergence and interoperability of semiconductor synthetic biology, engineering biology and other emerging frontiers. After going through the above four development stages, a number of synthetic biology companies have grown up, and many traditional pharmaceutical companies have also invested in the field of synthetic biology for drug development, generating a variety of patents related to gene synthesis, gene therapy, cell therapy, biological materials, genome editing, et al. Through the analysis of representative synthetic biology enterprises' product development and their corresponding patent layout, we highlight the main technical modules and application fields of synthetic biology technologies. Based on the systematic analysis of these key technologies and patents, we develope a break-up and comprehensive analysis framework to clarify the characteristics of synthetic biology for competitive landscapes and predict their technological trends. Especially, we developed a synthetic biology knowledge map to systematically present a landscape for synthetic biology development. By translating patent information into competitive intelligence, this study also investigated the impact of synthetic biology applications on various aspects of industry and society. Finally, this article summarizes and speculates the development of synthetic biology, including the development of enabling technology platforms and tools, definition and use of standard essential patents (SEPs), and relationship between intellectual property management and product accessment.

    Table and Figures | Reference | Related Articles | Metrics
    Application of dynamic regulation strategies in metabolic engineering
    Zheng Yu, Xiaolin SHEN, Xinxiao Sun, Jia Wang, Qipeng Yuan
    Synthetic Biology Journal    2020, 1 (4): 440-453.   DOI: 10.12211/2096-8280.2020-029
    Abstract2356)   HTML199)    PDF(pc) (2194KB)(3223)       Save

    As a sustainable biochemical reactor, microbial cell factories are widely used in the production of value-added compounds such as natural products, pharmaceuticals and nutraceuticals. In order to make microbial cell factories produce target compounds with high titer, productivity and yield, metabolic engineering strategies are employed to rationally modify and regulate their metabolism. However, knockout and overexpression of genes inevitably bring stresses such as redox imbalance and toxic intermediate accumulation. While dynamic control strategy has been proven as a promising tool to address these challenges by balancing carbon flux and energy generation and dissipation for cell growth and generation of target compounds. As a result, many dynamic regulation elements and gene circuits have been developed and widely used in metabolic engineering so far. In this review, we summarize four types of attractive dynamic regulation systems based on metabolite-response, quorum sensing-response, environmental parameter-response and protein level regulation, with a focus on the construction method of various regulatory elements and their applications in metabolic engineering. In addition, challenges faced by different dynamic control strategies in industrial applications are analyzed. At the same time, we prospect the application potentials of some strategies such as high-throughput screening, protein engineering, computer simulation and mathematical model analysis coupled with gene control elements in solving the problems of narrow response threshold and limited control range of dynamic regulation tools. With the further development of synthetic biology and metabolic engineering, we believe that dynamic control strategy will be widely used for the construction of microbial cell factories in the near future.

    Reference | Related Articles | Metrics
    Present and future of plant synthetic biology
    Jie SHAO, Haili LIU, Yong WANG
    Synthetic Biology Journal    2020, 1 (4): 395-412.   DOI: 10.12211/2096-8280.2020-037
    Abstract2311)   HTML189)    PDF(pc) (2353KB)(1719)       Save

    Benefiting from advances in systems biology and molecular biology, synthetic biology studies have been moving to more complicated multicellular systems. Therefore, plant synthetic biology is regarded as another hot spot for synthetic biology. Plants have rich endomembrane systems and organelles, highly specialized biosynthetic gene clusters and sophisticated metabolic regulation networks, which can serve as an ideal model system for research to address various challenges. Synthetic biology research carried out for plant chassis,such as designing sensors to detect environmental changes, developing precise genome editing techniques, and establishing efficient heterologous metabolic pathways, will not only facilitate our understanding of life, but also provide a novel strategy to address challenges in agriculture, biopharmaceutics, energy, environment, etc. for sustainable development. In addition to summarizing the latest progress in fundamentals with plant synthetic biology, which mainly involves the quantitative characterization and standardization of building blocks, rational design of genetic devices and development of enabling technologies, this article also reviews the practical application of this field in agriculture and industry, highlighting challenges that need to be solved at present and perspective applications in the future to provide an inspiration for researchers.

    Reference | Related Articles | Metrics
    Progress and perspectives on developing Zymomonas mobilis as a chassis cell
    Yongfu YANG, Binan GENG, Haoyue SONG, Qiaoning HE, Mingxiong HE, Jie BAO, Fengwu BAI, Shihui YANG
    Synthetic Biology Journal    2021, 2 (1): 59-90.   DOI: 10.12211/2096-8280.2020-071
    Abstract2276)   HTML179)    PDF(pc) (4923KB)(2206)       Save

    Zymomonas mobilis, the only microorganism known to use the Entner-Doudoroff (ED) pathway anaerobically, can produce ethanol naturally from glucose, fructose and sucrose with many desirable traits such as ethanol production at high rate and yield and merit with biosafety (generally regarded as safe, GRAS), which has attracted more attention to be engineered as cell factories to produce biofuels and other bio-based products from lignocellulosic biomass. With the rapid development of novel technologies such as next-generation sequencing (NGS) and CRISPR-Cas genome editing as well as the accumulation of knowledge from studies on its physiology and modifications through metabolic engineering and systems biology, it is necessary to summarize accomplishments achieved recently to further explore the advantages of Z. mobilis, expediting the development and deployment of the robust synthetic microbial chass for the goals of "build to understand" and "build to apply" in the systems and synthetic biology era. In this review, we critically comment on the unique physiological characteristics of Z. mobilis and its potentials as a synthetic chassis to be engineered as microbial cell factories for producing diverse biochemicals economically, with a focus on the advances and challenges of developing efficient and effective tools and techniques for engineering this bacterium, taking advantages of methodologies developed with system biology and synthetic biology as well as metabolic engineering. We also prospect on future research for developing Z. mobilis as an attractive microbial chassis to be able to fix CO2 and N2 for biochemical production through genome optimization and metabolic engineering to advance the principles of synthetic biology and explore its potentials on biotechnological applications, which need unceasing effort to improve, develop and deploy efficient and effective genome editing tools, strategies for fine-tuning metabolic and regulatory pathways timely and spatially, as well as automatic high-throughput screening and quantification approaches.

    Reference | Related Articles | Metrics
    Reading, editing, and writing techniques for genome research
    Hui WANG, Junbiao DAI, Zhouqing LUO
    Synthetic Biology Journal    2020, 1 (5): 503-515.   DOI: 10.12211/2096-8280.2020-013
    Abstract2244)   HTML240)    PDF(pc) (2023KB)(2533)       Save

    Genome carries the entire genetic information of life. Genome-related researches are ultimate fundamentals for life sciences. Technological development in genomic researches has deepened our understanding of genomes and their function. Obtaining genome sequences through sequencing, studying their function and regulation through editing and creating customer designed genomes through synthesis are three important aspects of genome research. From the first-generation sequencing to the third-generation sequencing, the "reading" technology has greatly reduced the cost and difficulty, while improved the speed, enabling the production of complete genomic information for complex and large genomes. From random mutagenesis to site-specific genome editing and, from ZFN to CRISPR, the genome "editing" technology has improved significantly in efficiency, applicability, and simplicity, providing a wealth of materials to dissect "genotype-phenotype" relationship. Accurate editing and high-throughput editing are moving towards applications in various areas. From viral genome, bacterial genome to yeast genome, and ultimately to human genome, synthetic genomics has moved from simple organisms to many complex organisms. Precise, fast and low-cost synthesis technologies are important for the development of synthetic genomics. This article reviews the histories, features, present status, and applications of technologies for genome sequencing (reading), genome editing (editing) and genome synthesizing (writing). The potential breakthrough of these technologies in the near future is also summarized and prospected. The ability to read, edit and write a genome has been and will continue to advance not only our understanding but also better utilization of living systems.

    Reference | Related Articles | Metrics