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Table of Content

    30 April 2020, Volume 1 Issue 2
    Contents
    2020, 1(2):  0-0. 
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    Invited Review
    Recent advances in plant synthetic biology
    Bo ZHANG, Yongshuo MA, Yi SHANG, Sanwen HUANG
    2020, 1(2):  121-140.  doi:10.12211/2096-8280.2020-016
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    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.

    Applications of synthetic biology in the treatment and prevention of infectious diseases
    Lu PU, Yajia HUANG, Shuai YANG, Fan JIN
    2020, 1(2):  141-157.  doi:10.12211/2096-8280.2020-021
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    Synthetic biology is bringing together engineers and biologists to design and create novel biological blocks, networks and pathways, which are used to construct, rewire and reprogram organisms. Over the past two decades, scientists have designed and built increasingly complex circuits and constructs for applications to a variety of settings, including biomedicine. Multidrug-resistant infections have emerged as a major threat to hospitalized patients due to the prevalent and often inappropriate use of broad-spectrum antibiotics, which are associated with the boost of mortality. The technologies of synthetic biology have contributed to the understanding of mechanism and provided design of novel strategies. In this review, we first describe CRISPR-Cas based technology for diagnostics, such as SHERLOCK and DETECTR, and then discuss engineered phages, bacteria and the strategies of synthetic biology for combating drug resistance and bacterial biofilms. Also, synthetic biology principle of ‘analysis by synthesis’ as well as CRISPR technology have been applied to unravel mechanism of viral infectious disease and to develop therapies. Finally, we summarize the applications of synthetic biology in prevention of infectious diseases, including engineered probiotic bacteria, vaccine development and control of infectious vectors.

    Advances in methanol bio-transformation
    Jiaoqi GAO, Yongjin ZHOU
    2020, 1(2):  158-173.  doi:10.12211/2096-8280.2020-017
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    Methanol represents a promising feedstock due to its specific characteristics for storage and transport, which has been widely applied in chemical industry as raw material, intermediate and fuel. Methanol bio-transformation by microbes may further expand the methanol-based production of high quality fuels and various chemicals, which will drive clean utilization of inferior coal and natural gas. We here review recent advances in methanol-based bio-refinery. We first summarize current progress in methanol production through chemical and biological processes, which shows that the chemical process is now the main route for methanol supply. However, emerging technologies like methane oxidation (chemical or biological) and CO2 hydrogenation may achieve a renewable, sustainable and clean route for methanol production. We then discuss the engineering of methylotrophs (bacterial and yeast) for producing a variety of chemicals from methanol (Top-Down approach), which indicates that improved genetic tools may further optimize these cell factories for industrial applications. We also summarize recent advances on engineering artificial methylotrophs in numerous model organisms such as Escherichia coli, Corynebacterium glutamicum and Saccharomyces cerevisiae (Bottom-Up approach). The advances in synthetic biology, metabolic engineering and adaptive laboratory evolution will facilitate the construction of robust microbial cell factories for methanol biotransformation, which will expand substrate resource for bio-refinery and the product portfolio of methanol.

    The past and present of vitamin E
    Tian MA, Zixin DENG, Tiangang LIU
    2020, 1(2):  174-186.  doi:10.12211/2096-8280.2020-022
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    Vitamin E, as one of the most important antioxidants in biological systems, has a variety of biological functions. For example, it can maintain normal metabolism and improve the fertility and immunity of humans and animals. It occupies an important position in the fields of medicine and feed. It is a basic supplemental product for people in China and also one of the three major vitamin products with big production volume and sale in the international market. Since it was developed in 1938, the synthesis technology of vitamin E has experienced a history of more than 80 years. With technological innovations, a relatively stable market has gradually formed for vitamin E. Here, we summarized the development of vitamin E synthesis technology, including extraction from natural resources and synthesis with chemical, biological and biochemical routes. The technologies of chemical and biochemical synthesis as the most competitive processes are introduced in details. The history of vitamin E is reviewed and the future development of vitamin E is prospected.

    Progress and prospect for synthetic biology research of the industrial filamentous fungi Aspergillus terreus
    Xuenian HUANG, Shen TANG, Xuefeng LV
    2020, 1(2):  187-211.  doi:10.12211/2096-8280.2020-002
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    Filamentous fungi are a class of important microorganisms, which have played an important role in the fields of industrial sectors and people's daily life for the production of food, medicine, and chemical products. With the development of synthetic biology, filamentous fungi have shown more potentials. Aspergillus terreus is an industrially valuable filamentous fungus, which has been applied in the production of the bio-based chemical itaconic acid and the lipid-lowering drug lovastatin. The excellent synthetic ability of natural products and outstanding fermentation properties of A. terreus have been fully demonstrated through industrial applications. Meanwhile, it has also been acknowledged that A. terreus would be a promising filamentous fungal chassis cell for synthetic biology development. In recent years, many studies have been performed using A. terreus, including genetic engineering of industrial strains, optimization of fermentation processes, elucidation of biosynthetic mechanisms, etc., which have significantly contributed to the development of A. terreus synthetic biology.

    Herewith, these recent research advances are reviewed from: 1) Synthetic biology tools for A. terreus. The development of genetic operation systems is introduced, including the characterization and application of promoters and markers and the progress of gene-editing technologies. 2) Industrial cell factory for the lipid-lowering drug lovastatin. In addition to the biosynthetic pathway of lovastatin, the design and construction of an efficient monacolin J-producing cell factory based on the industrial A. terreus strains are introduced in details. 3) Industrial cell factory for the bio-based chemical itaconic acid. The biosynthetic pathway of itaconic acid and the systematic metabolic engineering of the industrial strain are introduced. 4) Biosynthesis of secondary metabolites. The biosynthetic mechanism and research strategies for the secondary metabolites are introduced. 5) The advantages and prospects of A. terreus chassis cells in synthetic biology are summarized, and the practical applications are listed. Based on the research progress of A. terreus and other filamentous fungi, the challenges and future work of A. terreus biosynthesis technology development are proposed, including enriching the genetic element library, developing efficient gene editing methods and building high-throughput evaluation platforms. Addressing these challenges will provide more alternative design strategies for building more efficient cell factories of A. terreus, and will also contribute to promoting synthetic biology research of filamentous fungi.

    Compatibility between synthetic pathway and chassis cells from the viewpoint of post-translational modifications
    Di YOU, Bangce YE
    2020, 1(2):  212-225.  doi:10.12211/2096-8280.2020-006
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    The complexity of chassis cell influences the effectiveness of synthetic constructs and resource allocation. The effect of regulatory systems on the engineered biosynthetic pathways in microorganisms remains incompletely understood. Acyl-CoAs function as key precursors for the biosynthesis of various natural products as well as the dominant donors for protein acylation. Increasing supply of acyl-CoAs contributes to the increased yield, while oversupply also leads to an increase in the global acylation level thereby decreasing the biosynthesis of natural products. Here we provide an overview of the host-construct interactions in the view of the intricate balance of cellular concentrations for acyl-CoAs and the yields of acyl-CoAs-derived products. In particular, we highlight the application of post-translational modification metabolic engineering (PTM-ME) on the biosynthesis of erythromycin, butanol and pinosylvin biosynthesis via raising acyl-CoAs supply, and in the same time bypassing the feedback inhibition caused by acylation. In conclusion, the system-level understanding of PTM with proteins offers a conceptual and technological framework for creating new metabolic enzymes/pathways to optimize the optimal production of desired products.

    Applications of the multienzyme-catalyzed tandem strategy in the synthesis of complex natural products
    Junbin HE, Song MENG, Haixue PAN, Gongli TANG
    2020, 1(2):  226-246.  doi:10.12211/2096-8280.2020-010
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    Structurally diverse natural products and their derivatives have been an indispensable source for the discovery of new drugs. However, the traditional extraction, isolation and characterization of natural products from animals, plants and microorganisms often have challenges such as low efficiency, time-consuming and expensive cost, which greatly hinder their development as new drugs. The complete synthesis of natural products mainly includes chemical synthesis and biosynthesis. Among them, In vitro enzymatic synthesis has the advantages of high catalytic efficiency, high chemo-, stereo- and regio-selectivity, specific product spectrum, simple and mild reaction conditions and environmental friendly, which make it an effective strategy for the synthesis of complex natural products. This paper reviews recent research advances in the synthesis of complex natural products by in vitro enzymatic methods, especially the applications of the multienzyme-catalyzed tandem strategy for synthesis of complex natural products including polyketides, alkaloids, terpenoids, steroids, macrolides and nucleosides. Furthermore, the bottlenecks, corresponding solutions and the perspective of this strategy are discussed.

    Advances in design, construction and applications of Bacillus subtilis chassis cells
    Lu LIN, Xueqin LV, Yanfeng LIU, Guocheng DU, Jian CHEN, Long LIU
    2020, 1(2):  247-265.  doi:10.12211/2096-8280.2020-030
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    As a model industrial host and an important generally recognized as safe microorganism, Bacillus subtilis has been used for a wide range of applications such as the industrial production of enzymes and nutraceuticals. In recent years, with the elucidation of the genetic regulation mechanism of B. subtilis, various research strategies and technologies have been designed and developed with this chassis, including gene editing, gene circuits, spatial biomolecular scaffold and cell-free expression systems. In this review, we start with systematic summaries on the construction of B. subtilis chassis based on gene editing systems and endogenous regulatory mechanisms. Then applications of B. subtilis cell factories are discussed for producing N-acetylglucosamine, menaquinone-7, riboflavin, hyaluronic acid and β-cyclodextrin glycosyltransferase. Finally, prospects for the design, construction and applications of engineered B. subtilis strains are commented, with an emphasis on improving genome editing efficiency, expanding responsive metabolite spectrum for genetic circuits, and rewiring the whole genome.