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Table of Content
28 February 2021, Volume 29 Issue 2
    The production of biobased diamines from renewable carbon sources: Current advances and perspectives
    Xin Wang, Siyuan Gao, Jing Wang, Sheng Xu, Hui Li, Kequan Chen, Pingkai Ouyang
    2021, 29(2):  4-13.  doi:10.1016/j.cjche.2020.12.009
    Abstract ( 104 )   PDF (2200KB) ( 201 )  
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    Bio-based diamines are considered to be a promising alternative to traditional fossil-fuel-based diamines, the important platform chemical for the synthesis of polymer materials. In this review, the current status of the art of the synthesis of aliphatic and aromatic diamines from renewable biomass are considered. In the case of aliphatic diamines, we describe strategies for biologically producing diamines with different carbon numbers including 1,3-diaminopropane, 1,4-butanediamine, 1,5-pentanediamine, 1,6-diaminohexane, 1,8-diaminooctane, 1,10-diaminodecane, and 1,12-diaminododecane. In addition, aromatic diamines produced from various kinds of renewable biomass, including lignin, cashew nut shell, and terpenoids, are reviewed here. Furthermore, the application of typical diamines in synthesis of polyurethane and polyamide are also reviewed.
    Efficient production of chemicals from microorganism by metabolic engineering and synthetic biology
    Yang Zhang, Jing Yu, Yilu Wu, Mingda Li, Yuxuan Zhao, Haowen Zhu, Changjing Chen, Meng Wang, Biqiang Chen, Tianwei Tan
    2021, 29(2):  14-28.  doi:10.1016/j.cjche.2020.12.014
    Abstract ( 59 )   PDF (6805KB) ( 76 )  
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    The use of traditional chemical catalysis to produce chemicals has a series of drawbacks, such as high dependence on fossil resources, high energy consumption, and environmental pollution. With the development of synthetic biology and metabolic engineering, the use of renewable biomass raw materials for chemicals synthesis by constructing efficient microbial cell factories is a green way to replace traditional chemical catalysis and traditional microbial fermentation. This review mainly summarizes several types of bulk chemicals and high value-added chemicals using metabolic engineering and synthetic biology strategies to achieve efficient microbial production. In addition, this review also summarizes several strategies for effectively regulating microbial cell metabolism. These strategies can achieve the coupling balance of material and energy by regulating intracellular material metabolism or energy metabolism, and promote the efficient production of target chemicals by microorganisms.
    Food synthetic biology-driven protein supply transition: From animal-derived production to microbial fermentation
    Yanfeng Liu, Xiaomin Dong, Bin Wang, Rongzhen Tian, Jianghua Li, Long Liu, Guocheng Du, Jian Chen
    2021, 29(2):  29-36.  doi:10.1016/j.cjche.2020.11.014
    Abstract ( 148 )   PDF (1035KB) ( 137 )  
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    Animal-derived protein production is one of the major traditional protein supply methods, which continues to face increasing challenges to satisfy global needs due to population growth, augmented individual protein consumption, and aggravated environmental pollution. Thus, ensuring a sustainable protein source is a considerable challenge. The emergence and development of food synthetic biology has enabled the establishment of cell factories that effectively synthesize proteins, which is an important way to solve the protein supply problem. This review aims to discuss the existing problems of traditional protein supply and to elucidate the feasibility of synthetic biology in the process of protein synthesis. Moreover, using artificial bioengineered milk and artificial bioengineered eggs as examples, the progress of food protein supply transition based on synthetic biology has been systematically summarized. Additionally, the future of food synthetic biology as a potential source of protein has been also discussed. By strengthening and innovating the application of food synthetic biology technologies, including genetic engineering and high-throughput screening methods, the current limitations of artificial foods for protein synthesis and production should be addressed. Therefore, the development and industrial production of new food resources should be explored to ensure safe, high-quality, and sustainable global protein supply.
    A comparative analysis of China and other countries in metabolic engineering: Output, impact and collaboration
    Cong Chen, Tao Chen, Zhiwen Wang, Xueming Zhao
    2021, 29(2):  37-45.  doi:10.1016/j.cjche.2020.12.007
    Abstract ( 48 )   PDF (5796KB) ( 31 )  
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    In recent years, metabolic engineering has made great progress in both academic research and industrial applications. However, we have not found any articles that specifically analyze the current state of metabolic engineering in China in comparison with other countries. Here, we review the current development and future trends of global metabolic engineering, conduct an in-depth benchmarking analysis of the development situation of China’s metabolic engineering, and identify current problems as well as future trends. We searched publications in the Scopus database from 2015 to September 2020 in the field of metabolic engineering, and analyzed the output in general, including publication trends, research distribution, popular journals, hot topics and vital institutions, but also analyzed the share of citations, field-weighted citation impact, and production in collaboration with strategic countries in science and technology. This study aims to serve as a reference for later studies, offering a comprehensive view of China’s contribution to metabolic engineering, and as a tool for the elaboration of national public policy in science and technology.
    Impact of oxygen supply on production of terpenoids by microorganisms: State of the art
    Ting-Ting Liu, Han Xiao, Jian-Hui Xiao, Jian-Jiang Zhong
    2021, 29(2):  46-53.  doi:10.1016/j.cjche.2020.12.006
    Abstract ( 76 )   PDF (1744KB) ( 59 )  
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    Terpenoids are a class of high value-added natural products with a variety of biological functions. Genetically engineered microorganisms, such as those of Escherichia coli and Saccharomyces cerevisiae, have merits in producing plant or fungus-derived terpenoids, due to their mature genetic manipulation, simple nutrient demand and fast growth. Oxygen, as a key environmental factor, is particularly important to microbial metabolism and growth, and suitable oxygen supply is viewed as a prerequisite for realizing highly efficient production of terpenoids by engineered microorganisms. In this article, the role of oxygen in regulating terpenoid bioproduction is overviewed from the viewpoints of cellular carbon metabolism, energy metabolism and terpenoid anabolism. Strategies on adjusting oxygen availability to microorganisms, including genetic modification of cellular metabolism related with oxygen utilization, are summarized and discussed, to provide helpful information for further improvement of terpenoid biosynthesis by microbes.
    Recent advances in microbial production of phenolic compounds
    Xinxiao Sun, Xianglai Li, Xiaolin Shen, Jia Wang, Qipeng Yuan
    2021, 29(2):  54-61.  doi:10.1016/j.cjche.2020.09.001
    Abstract ( 58 )   PDF (3430KB) ( 69 )  
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    Phenolic compounds (PCs) are a group of compounds with various applications in nutraceutical, pharmaceutical and cosmetic industries. Their supply by plant extraction and chemical synthesis is often limited by low yield and high cost. Microbial production represents as a promising alternative for efficient and sustainable production of PCs. In this review, we summarize recent advances in this field, which include enzyme mining and engineering to construct artificial pathways, balance of enzyme expression to improve pathway efficiency, coculture engineering to alleviate metabolic burden and side-reactions, and the use of genetic circuits for dynamic regulation and high throughput screening. Finally, current challenges and future perspectives for efficient production of PCs are also discussed.
    Engineered microorganisms and enzymes for efficiently synthesizing plant natural products
    Wenqiang Li, Wentao Sun, Chun Li
    2021, 29(2):  62-73.  doi:10.1016/j.cjche.2020.12.015
    Abstract ( 105 )   PDF (3997KB) ( 95 )  
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    Plant natural products are a kind of active substance widely used in pharmaceuticals and foods. However, the current production mode based on plant culture and extraction suffer complex processes and severe concerns for environmental and ecological. With the increasing awareness of environmental sustainability, engineered microbial cell factories have been an alternative approach to produce natural products. Many engineering strategies have been utilized in microbial biosynthesis of complex phytochemicals such as dynamic control and substructure engineering. Meanwhile, Enzyme engineering including directed evolution and rational design has been implemented to improve enzyme catalysis efficiency and stability as well as change promiscuity to expand product spectra. In this review, we discussed recent advances in microbial biosynthesis of complex phytochemicals from the following aspects, including pathway construction, strain engineering to boost the production.
    Recombinant protein production in the filamentous fungus Trichoderma
    Huiling Wei, Mengyue Wu, Aili Fan, Haijia Su
    2021, 29(2):  74-81.  doi:10.1016/j.cjche.2020.11.006
    Abstract ( 110 )   PDF (4148KB) ( 113 )  
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    Trichoderma is an ascomycete fungal genus widely distributed in the soils. Several species were selected, engineered and utilized for protein production for decades. The high extracellular secretion capability and eukaryotic post-translational modification machinery make Trichoderma spp. particularly interesting hosts. In this review, we summarized the recombinant proteins produced in Trichoderma since 2014, concerning their origins, hosts, promoters, terminators, signal peptides, yields and commonly used media. Meanwhile, strategies and merging trends in protein production and strain engineering are classified and summarized regarding codon optimization, promoter utilization, transcription factor regulation, post-translational modification and proteolytic degradation inhibition. With state-of-art biotechnologies and more available expression platforms, Trichoderma spp. could be more successful hosts to produce recombinant proteins as desired, i.e. better enzyme formula for efficient cellulose degradation or functional protein with high purity and yield.
    Deciphering and engineering high-light tolerant cyanobacteria for efficient photosynthetic cell factories
    Yaru Xie, Lei Chen, Tao Sun, Weiwen Zhang
    2021, 29(2):  82-91.  doi:10.1016/j.cjche.2020.11.002
    Abstract ( 84 )   PDF (2206KB) ( 186 )  
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    Development and utilization of “liquid sunshine” could be one of key solutions to deal with the issues of fossil fuel depletion and increasing carbon dioxide. Cyanobacteria are the only prokaryotes capable of performing oxygenic photosynthesis, and their activity accounts for ~25% of the total carbon fixation on earth. More importantly, besides their traditional roles as primary producers, cyanobacteria could be modified as “photosynthetic cell factories” to produce renewable fuels and chemicals directly from CO2 driven by solar energy, with the aid of cutting-edging synthetic biology technology. Towards their large-scale biotechnological application in the future, many challenges still need to be properly addressed, among which is cyanobacterial cell factories inevitably suffer from high light (HL) stress during large-scale outdoor cultivation, resulting in photodamage and even cell death, limiting their productivity. In this review, we critically summarized recent progress on deciphering molecular mechanisms to HL- and developing HL-tolerant chassis in cyanobacteria, aiming at facilitating construction of HLresistant chassis and promote the future application of the large-scale outdoor cultivation of cyanobacterial cell factories. Finally, the future directions on cyanobacterial chassis engineering were discussed.
    A review on current conventional and biotechnical approaches to enhance biosynthesis of steviol glycosides in Stevia rebaudiana
    Samra Basharat, Ziyang Huang, Mengyue Gong, Xueqin Lv, Aqsa Ahmed, Iftikhar Hussain, Jianghua Li, Guocheng Du, Long Liu
    2021, 29(2):  92-104.  doi:10.1016/j.cjche.2020.10.018
    Abstract ( 180 )   PDF (5167KB) ( 264 )  
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    Stevia rebaudiana Bertoni is commonly called stevia and mostly found in the north east regions of South America. It is an herbaceous and shrubby plant belonging to the Asteraceae family. Stevia is considered as a natural sweetener and a commercially important plant worldwide. The leaves of S. rebaudiana contain steviol glycosides (SGs) which are highly potent and non-caloric sweeteners. The sweetening property of S. rebaudiana is contributed to the presence of these high potency, calorie free steviol glycosides. SGs are considerably suitable for replacing sucrose and other artificial sweetening agents which are used in different industries and pharmaceuticals. SGs amount in the plant mostly varies from 8% to 10%, and the enhancement of SGs is always in demand. These glycosides have the potential to become healthier alternatives to other table sugars for having desirable taste and zero calories. SGs are almost 300 times sweeter than sucrose. Being used as alternative sugar intensifier the commercial value of this plant in biopharmaceutical, food and beverages industries and in international market is increasing day by day. SGs have made stevia an important part of the medicinal world as well as the food and beverage industry, but the limited production of plant material is not fulfilling the higher global market demand. Therefore, researchers are working worldwide to increase the production of important SGs through the intercession of different biotechnological approaches in S. rebaudiana. This review aims to describe the emerging biotechnological strategies and approaches to understand, stimulate and enhance biosynthesis of secondary metabolites in stevia. Conventional and biotechnological methods for the production of steviol glycosides have been briefly reviewed and discussed.
    Microbial production of L-malate from renewable non-food feedstocks
    Youming Jiang, Xiaohan Ye, Tianwen Zheng, Weiliang Dong, Fengxue Xin, Jiangfeng Ma, Min Jiang
    2021, 29(2):  105-111.  doi:10.1016/j.cjche.2020.10.017
    Abstract ( 80 )   PDF (952KB) ( 44 )  
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    L-malate is an intermediate of the tricarboxylic acid cycle which is naturally occurred in various microorganisms, and it has been widely applied in polymer, beverage and food, textile, agricultural and pharmaceutical industries. Driven by the pursuit of a sustainable economy, microbial production of L-malate has received much attention in last decades. In this review, we focus on the utilization of wastes and/or byproducts as feedstocks for the microbial production of L-malate. Firstly, we present the recent developments on the natural or engineered metabolic pathways that dedicate to the biosynthesis of L-malate, and also provide a comprehensive discussions on developing high-efficient producers. Then, the recent achievements in microbial production of L-malate from various carbon sources were concluded and discussed. Furthermore, some abundant non-food feedstocks which have been used for microbial production of other chemicals were reviewed, as they may be potential candidate feedstock for L-malate production in future. Finally, we outlined the major challenges and proposed further improvements for the production of L-malate.
    Insights into constructing a stable and efficient microbial consortium
    Chunmeng Xu, Huimin Yu
    2021, 29(2):  112-120.  doi:10.1016/j.cjche.2020.12.012
    Abstract ( 111 )   PDF (3724KB) ( 190 )  
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    Microbial consortia are ubiquitous in nature, in which multiple microbial species cooperate to complete some important tasks such as lignocellulose degradation. Because of the advantages such as reduced metabolic burden and robustness to environment disturbances, developing a microbial consortium is a promising approach for valuable product synthesis, lignocellulose utilization, human health care, bioremediation and sustainable energy, etc. Despite the benefits, however, most artificial microbial consortia confront the problems of instability and low efficiency due to growth competition and metabolite incompatibility. To overcome these challenges, multiple strategies to design efficient synthetic microbial consortia have been reported. In this review, the interactions that determine the stability and performance of microbial consortia were described. Progress of artificial microbial consortia research was summarized, and the key strategies i.e., spatial or temporal segregation, separated utilization of nutrients, nutrient cross-feeding and division of labor, that will be of great importance for achieving a stable and efficient microbial consortium were highlighted. Two novel advanced tools, signaling molecule systems and computational models, were also introduced and discussed. We believed that combining the universal cell–cell signaling molecule systems with computational models will be promising for synthetic microbial consortia construction in the future.
    Self-sufficient Cytochrome P450s and their potential applications in biotechnology
    Bekir Engin Eser, Yan Zhang, Li Zong, Zheng Guo
    2021, 29(2):  121-135.  doi:10.1016/j.cjche.2020.12.002
    Abstract ( 118 )   PDF (1967KB) ( 110 )  
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    Cytochrome P450s (CYPs) are ubiquitously found in all kingdoms of life, playing important role in various biosynthetic pathways as well as degradative pathways; accordingly find applications in a vast variety of areas from organic synthesis and drug metabolite production to modification of biomaterials and bioremediation. Significantly, CYPs catalyze chemically challenging C—H and C—C activation reactions using a reactive high-valent iron-oxo intermediate generated upon dioxygen activation at their heme center, while the other oxygen atom is reduced to the level of water by electrons provided through a reductase partner protein. Self-sufficient CYPs, encoding their heme domain and reductase protein in a single polypeptide, facilitate increased catalytic efficiency and render a less complicated system to work with. The self-sufficient CYP enzyme from CYP102A family (CYP102A1, BM3) is among the earliest and most-investigated model enzymes for mechanistic and structural studies as well as for biotechnological applications. An increasing number of self-sufficient CYPs from the same CYP102 family and from other families have also been reported in last decade. In this review, we introduce chemistry and biology of CYPs, followed by an overview of the characteristics of self-sufficient CYPs and representative reactions. Enzyme engineering efforts leading to novel self-sufficient CYP variants that can catalyze synthetically useful natural and non-natural (nature-mimicking) reactions are highlighted. Lastly, the strategy and efforts that aim to circumvent the challenges for improved thermostability, regio-and enantioselectivity, and total turnover number; associated with practical use of self-sufficient CYPs are reviewed.
    Microfluidic reactor with immobilized enzyme-from construction to applications: A review
    Han Zhang, Yunpeng Bai, Ning Zhu, Jianhe Xu
    2021, 29(2):  136-145.  doi:10.1016/j.cjche.2020.12.011
    Abstract ( 129 )   PDF (2211KB) ( 152 )  
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    Microfluidic, as the systems for using microchannel (micron-or sub-micron scale) to process or manipulate microflow, is being widely applied in enzyme biotechnology and biocatalysis. Microfluidic immobilized enzyme reactor (MIER) is a tool with great value for the study of catalytic property and optimal reaction parameter in a flourishing and highly producing manner. In view of its advantages in efficiency, economy, and addressable recognition especially, MIER occupies an important position in the investigation of life science, including molecular biology, bioanalysis and biosensing, biocatalysis etc. Immobilization of enzymes can generally improve their stability, and upon most occasions, the immobilized enzyme is endowed with recyclability. In this review, the enzyme immobilization techniques applied in MIER will be discussed, followed by summarizing the novel developments in the field of MIER for biocatalysis, bioconversion and bioanalysis. The preponderances and deficiencies of the current state-of-the-art preparation ways of MIER are peculiarly discussed. In addition, the prospects of its future study are outlined.
    Recent advance of chemoenzymatic catalysis for the synthesis of chemicals: Scope and challenge
    Mengjiao Xu, Zhuotao Tan, Chenjie Zhu, Wei Zhuang, Hanjie Ying, Pingkai Ouyang
    2021, 29(2):  146-167.  doi:10.1016/j.cjche.2020.12.016
    Abstract ( 49 )   PDF (13465KB) ( 15 )  
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    Chemoenzymatic catalysis can give full play to the advantages of versatile reactivity of chemocatalysis and excellent chemo-, regio-, and stereoselectivities of biocatalysis. These chemoenzymatic methods can not only save resource, cost, and operating time but also reduce the number of reaction steps, and avoid separating unstable intermediates, leading to the generation of more products under greener circumstances and thereby playing an indispensable role in the fields of medicine, materials and fine chemicals. Although incompatible challenges between chemocatalyst and biocatalyst remain, strategies such as biphasic system, artificial metalloenzymes, immobilization or supramolecular host, and protein engineering have been designed to overcome these issues. In this review, chemoenzymatic catalysis according to different chemocatalysis types was classifiably described, and in particular, the classic dynamic kinetic resolutions (DKR) and cofactor regeneration were summarized. Finally, the bottlenecks and development of chemoenzymatic catalysis were summarized, and future development was prospected.
    Recent advances in detoxification strategies for zearalenone contamination in food and feed
    Na Wu, Wen Ou, Zhidong Zhang, Yuwen Wang, Qing Xu, He Huang
    2021, 29(2):  168-177.  doi:10.1016/j.cjche.2020.11.011
    Abstract ( 128 )   PDF (1851KB) ( 196 )  
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    Zearalenone (ZEN) is a widely distributed mycotoxin that frequently contaminates crops and animal feed. ZEN can cause serious health problems in livestock and humans alike, leading to great economic losses in the food industry and livestock farming. Therefore, approaches for efficient ZEN decontamination in food and feed are urgently needed. Traditional physical and chemical methods may decrease the nutritional quality of food and palatability of feed, or leading to residues and safety concerns. By contrast, biological methods for the removal or degradation of ZEN overcome these problems, especially for biological degradation by microorganisms and specific enzymes extracted from strains that can convert ZEN to less toxic or even completely harmless products. In this review, we comprehensively describe methods for ZEN degradation, focusing especially on biological strategies. Finally, emerging strategies and advice on remaining challenges in biodegradation research are also briefly discussed.
    Understanding the scale-up of fermentation processes from the viewpoint of the flow field in bioreactors and the physiological response of strains
    Jianye Xia, Guan Wang, Meng Fan, Min Chen, Zeyu Wang, Yingping Zhuang
    2021, 29(2):  178-184.  doi:10.1016/j.cjche.2020.12.004
    Abstract ( 71 )   PDF (2002KB) ( 89 )  
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    The production capability of a fermentation process is predominately determined by individual strains, which ultimately affected ultimately by interactions between the scale-dependent flow field developed within bioreactors and the physiological response of these strains. Interpreting these complicated interactions is key for better understanding the scale-up of the fermentation process. We review these two aspects and address progress in strategies for scaling up fermentation processes. A perspective on how to incorporate the multiomics big data into the scale-up strategy is presented to improve the design and operation of industrial fermentation processes.
    Ionic liquid-based salting-out extraction of bio-chemicals
    Jianying Dai, Yaqin Sun, Zhilong Xiu
    2021, 29(2):  185-193.  doi:10.1016/j.cjche.2020.11.004
    Abstract ( 62 )   PDF (7117KB) ( 48 )  
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    Ionic liquids (ILs) are known as green solvents, and have been widely used in the dissolution and transformation of biopolymers, the extraction of bioactive compounds and metal ions, and the capture of SO2 or CO2. However, less attention was given to the separation of bio-based chemicals, such as diols and organic acids. Bio-based chemicals can be efficiently separated by organic solvent-based salting-out extraction (SOE) from fermentation broths, while organic solvents are normally unfriendly to environment and process safety in commercialized production due to their toxicity or/and flammability. In recent years, the IL-based SOE system has been explored in the separation of bio-based chemicals as an alternative of organic solvent-based SOE system. In this review, the progress of IL-based SOE of biobased chemicals has been summarized, including the effect of ILs structure on the formation of aqueous two phases, and the influences of ILs structure and concentration, temperature and pH on the partition behaviors of target products and ILs as well as removal of impurities. Most of bio-based chemicals could be distributed into the IL-rich phase with high recovery, while the partition behaviors of bio-based chemicals are sometimes different from that in organic solvent-based SOE systems. Although the results of ILbased SOE are promising, further studies are still required in the increased selectivity of target products over by-products, recovery and recycling of ILs, and the separation between ILs and bio-based chemicals. Additionally, three kinds of integrated bioprocesses would be developed on basis of utilization of ILs as extractant for SOE, catalyst for condensation reaction and solvent for pretreatment of lignocellulose.
    Protein A-based ligands for affinity chromatography of antibodies
    Qinghong Shi, Yan Sun
    2021, 29(2):  194-203.  doi:10.1016/j.cjche.2020.12.001
    Abstract ( 76 )   PDF (3682KB) ( 146 )  
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    Protein A chromatography is a key technology in the industrial production of antibodies, and a variety of commercial protein A adsorbents are available in shelf. High stability and binding capacity of a protein A adsorbent are two key issues for successful practice of protein A chromatography. Earlier versions of protein A adsorbents ever exhibited serious fragility to typical cleaning-in-place protocols (e.g. washing with sodium hydroxide solution), and suffered from low binding capacity, harsh elution, ligand leakage and other problems involved in industrial applications. During the last three decades, various techniques and approaches have been applied in the improvement of chemical stability and enhancement of binding capacity of protein A-based ligands and adsorbents for antibody purifications. This mini-review focuses on the technical explorations in protein A-based affinity adsorbents, especially protein A-based ligands, including the efforts to increase the chemical stability by site-directed mutations and to improve the binding capacity by ligand polymerization and site-directed immobilization. Moreover, the efforts to develop short peptide ligands based on the structure of protein A, including the biomimetic design strategies and the synthesis of peptide-mixed mode hybrid ligands are discussed. These peptide and peptidebased hybrid ligands exhibit high affinity and selectivity to antibodies, but noteworthy differences in the binding mechanism of antibody from protein A. As a result, bound antibody to the ligands could be effectively eluted under mild conditions. Perspectives for the development of the protein A-based peptide ligands have been extensively discussed, suggesting that the ligands represent a direction for technological development of antibody purification.
    Raman spectroscopy as process analytical tool in downstream processing of biotechnology
    Yu Kiat Lin, Hui Yi Leong, Tau Chuan Ling, Dong-Qiang Lin, Shan-Jing Yao
    2021, 29(2):  204-211.  doi:10.1016/j.cjche.2020.12.008
    Abstract ( 273 )   PDF (2514KB) ( 177 )  
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    Downstream processing or product recovery plays a vital role in the development of bioprocesses. To improve the bioprocess efficiency, some unconventional methods are much required. The continuous manufacturing in downstream processing makes the Process Analytical Technologies (PATs) as an important tool. Monitoring and controlling bioprocess are an essential factor for the principles of PAT and quality by design. Spectroscopic methods can apply to monitor multiple analytes in real-time with less sample processing with significant advancements. Raman spectroscopy is an extensively used technique as an analytical and research tool owing to its modest process form, non-destructive, non-invasive optical molecular spectroscopic imaging with computer-based analysis. Generally, its application is essential for the analysis and characterization of biological samples, and it is easy to operate with minimal sample. The innovation on various types of enhanced Raman spectroscopy was designed to enhance the Raman analytical technique. Raman spectroscopy could couple with chemometrics to provide reliable alternative analysis method of downstream process analysis. Thus, this review aims to provide useful insight on the application of Raman spectroscopy for PAT in downstream processing of biotechnology and Raman data analysis in biological fields.
    Single-molecule biotechnology for protein researches
    Xiaoyan Zhuang, Qian Wu, Aihui Zhang, Langxing Liao, Baishan Fang
    2021, 29(2):  212-224.  doi:10.1016/j.cjche.2020.10.031
    Abstract ( 52 )   PDF (18015KB) ( 19 )  
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    Cells employ proteins to perform metabolic functions and maintain active physiological state through charge transfer and energy conversion. These processes are carried out in a narrow space precisely and rapidly, which, no doubt, bring great difficulty for their detection and dissection. Fortunately, in recent years, the development and expansion of single-molecule technique in protein research make monitoring the dynamical changes of protein at single-molecule level a reality, which also provides a powerful tool for the further exploration of new phenomena and new mechanisms of life activities. This paper aims to summarize the working principle and essential achievements of single-molecule technique in protein research in recent five years. We focus on not only dissecting the difference of nanopores, atomic force microscope, scanning tunneling microscope, and optical tweezers technique, but also discussing the great significance of these single-molecule techniques in investigating intramolecular and intermolecular interactions, electron transport, and conformational changes. Finally, the opportunities and challenges of the single-molecule technique in protein research are discussed, which provide a new door for single-molecule protein research.
    Amyloid cross-seeding between Aβ and hIAPP in relation to the pathogenesis of Alzheimer and type 2 diabetes
    Yanxian Zhang, Yijing Tang, Dong Zhang, Yonglan Liu, Jian He, Yung Chang, Jie Zheng
    2021, 29(2):  225-235.  doi:10.1016/j.cjche.2020.09.033
    Abstract ( 105 )   PDF (4364KB) ( 107 )  
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    Amyloid cross-seeding of different amyloid proteins is considered as a highly possible mechanism for exacerbating the transmissible pathogenesis of protein misfolding disease (PMDs) and for explaining a molecular link between different PMDs, including Alzheimer disease (AD) and type 2 diabetes (T2D), AD and Parkinson disease (PD), and AD and prion disease. Among them, AD and T2D are the most prevalent PMDs, affecting millions of people globally, while Aβ and hIAPP are the causative peptides responsible for AD and T2D, respectively. Increasing clinical and epidemiological evidences lead to a hypothesis that the cross-seeding of Aβ and hIAPP is more biologically responsible for a pathological link between AD and T2D. In this review, we particularly focus on (i) the most recent and important findings of amyloid cross-seeding between Aβ and hIAPP from in vitro, in vivo, and in silico studies, (ii) a mechanistic role of structural compatibility and sequence similarity of amyloid proteins (beyond Aβ and hIAPP) in amyloid cross-seeding, and (iii) several current challenges and future research directions in this lessstudied field. Review of amyloid cross-seeding hopefully provides some mechanistic understanding of amyloidogenesis and inspires more efforts for the better design of next-generation drugs/strategies to treat different PMDs simultaneously.
    The potential of ionic liquids in biopharmaceutical engineering
    Xuan Lin, Zhiguo Su, Yanli Yang, Songping Zhang
    2021, 29(2):  236-243.  doi:10.1016/j.cjche.2020.11.015
    Abstract ( 53 )   PDF (3291KB) ( 84 )  
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    Biopharmaceuticals, such as proteins, peptides, nucleic acids and vaccines, bring about great hopes for the prevention and treatment of various diseases, but the industrialization of these products still faces challenges such as structural instability, inefficient bioactivity and low bioavailability. Ionic liquids (ILs), the marvelous solvent media with inimitable and tunable properties, may provide alternative solutions to overcome the above problems of biopharmaceutical industry. Progress has gradually been made through studies by combination of ILs with biomacromolecules. The applications involved the stabilization, protection, and delivery of biopharmaceuticals. Recent trends are being forwarded to using ILs in vaccines and nucleic acid drugs. However, challenges remain on the toxicity and safety issues. Besides, the cost of adding ILs to the benefits of biopharmaceuticals need to be considered.
    Engineering organoid microfluidic system for biomedical and health engineering: A review
    Yifan Xing, Junyu Liu, Xiaojie Guo, Haipeng Liu, Wen Zeng, Yi Wang, Chong Zhang, Yuan Lu, Dong He, Shaohua Ma, Yonghong He, Xin-Hui Xing
    2021, 29(2):  244-254.  doi:10.1016/j.cjche.2020.11.013
    Abstract ( 96 )   PDF (4627KB) ( 84 )  
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    In recent years, organoid technology, i.e., in vitro three-dimensional (3D) tissue culture, has attracted increasing attention in biomedical engineering. Organoids are cell complexes induced by differentiation of stem cells or organ-progenitor cells in vitro using 3D culture technology. They can replicate the key structural and functional characteristics of the target organs in vivo. With the opening up of this new field of health engineering, there is a need for engineering-system approaches to the production, control, and quantitative analysis of organoids and their microenvironment. Traditional organoid technology has limitations, including lack of physical and chemical microenvironment control, high heterogeneity, complex manual operation, imperfect nutritional supply system, and lack of feasible online analytical technology for the organoids. The introduction of microfluidic chip technology into organoids has overcome many of these limitations and greatly expanded the scope of applications. Engineering organoid microfluidic system has become an interdisciplinary field in biomedical and health engineering. In this review, we summarize the development and culture system of organoids, discuss how microfluidic technology has been used to solve the main technical challenges in organoid research and development, and point out new opportunities and prospects for applications of organoid microfluidic system in drug development and screening, food safety, precision medicine, and other biomedical and health engineering fields.
    Concepts, processing, and recent developments in encapsulating essential oils
    Qirui Tian, Weiqing Zhou, Qiong Cai, Guanghui Ma, Guoping Lian
    2021, 29(2):  255-271.  doi:10.1016/j.cjche.2020.12.010
    Abstract ( 60 )   PDF (13606KB) ( 12 )  
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    By the virtue of their olfactory, physicochemical, and biological characteristics, essential oils (EOs) have drawn wide attention as additives in daily chemicals like perfume or personal care products. Nevertheless, they are physicochemically unstable and susceptible to degradation or loss. Microencapsulation offers a feasible strategy to stabilize and prolong release of EO. This review summarizes the recognized benefits and functional properties of various preparation and characterization methods, wherein innovative fabrication strategies and their formation mechanisms are especially emphasized. Progress in combining detecting/measuring technologies with kinetic modelling are discussed, to give an integral approach of controlling the dynamic release of encapsulated EOs. Moreover, new development trends of EOs capsules are also highlighted.
    State of arts on the bio-synthesis of noble metal nanoparticles and their biological application
    Kok Bing Tan, Daohua Sun, Jiale Huang, Tareque Odoom-Wubah, Qingbiao Li
    2021, 29(2):  272-290.  doi:10.1016/j.cjche.2020.11.010
    Abstract ( 64 )   PDF (9610KB) ( 19 )  
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    Nanomaterials are materials in which at least one of the dimensions of the particles is 100 nm and below. There are many types of nanomaterials, but noble metal nanoparticles are of interest due to their uniquely large surface-to-volume ratio, high surface area, optical and electronic properties, high stability, easy synthesis, and tunable surface functionalization. More importantly, noble metal nanoparticles are known to have excellent compatibility with bio-materials, which is why they are widely used in biological applications. The synthesis method of noble metal nanoparticles conventionally involves the reduction of the noble metal salt precursor by toxic reaction agents such as NaBH4, hydrazine, and formaldehyde. This is a major drawback for researchers involved in biological application researches. Hence, the bio-synthesis of noble metal nanoparticles (NPs) by bio-materials via bio-reduction provides an alternative method to synthesize noble metal nanoparticles which are potentially non-toxic and safer for biological application. In this review, the bio-synthesis of noble metal nanoparticle including gold nanoparticle (AuNPs), silver nanoparticle (AgNPs), platinum nanoparticle (PtNPs), and palladium nanoparticle (PdNPs) are first discussed. This is followed by a discussion of these biosynthesized noble metal in biological applications including antimicrobial, wound healing, anticancer drug, and bioimaging. Based on these, it can be concluded that the study on bio-synthesized noble metal nanoparticles will expand further involving bio-reduction by unexplored bio-materials. However, many questions remain on the feasibility of bio-synthesized noble metal nanoparticles to replace existing methods on various biological applications. Nevertheless, the current development of the biological application by bio-synthesized noble metal NPs is still intensively ongoing, and will eventually reach the goal of full commercialization.
    Recent advances in systemic and local delivery of ginsenosides using nanoparticles and nanofibers
    Jing Zhao, Zhiguang Duan, Xiaoxuan Ma, Yannan Liu, Daidi Fan
    2021, 29(2):  291-300.  doi:10.1016/j.cjche.2020.11.012
    Abstract ( 78 )   PDF (6070KB) ( 155 )  
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    Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure, metabolism and immune function. Following the technological advances in isolation, purification and mass production, their mechanisms of action are gradually elucidated, providing solid basis for clinical applications. Ginseng extracts (total ginsenosides) and ginsenoside Rg3, CK, Rd have been marketed or entered clinical trials as drugs or dietary supplements. Despite the proven safety and efficacy of some ginsenosides, their applications are hindered by inferior pharmacokinetics such as low solubility, poor membrane permeability and metabolic instability. Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility, providing protection, facilitating intracellular transport, and enabling sustained and controlled release. This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes, micelles, albumin-based nanoparticles, and inorganic nanoparticles, as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.
    Monoclonal antibody-based cancer therapies
    Yingnan Si, Arin L. Melkonian, Keegan C. Curry, Yuanxin Xu, Maranda Tidwell, Mingming Liu, Ahmed F. Zaky, Xiaoguang (Margaret) Liu
    2021, 29(2):  301-307.  doi:10.1016/j.cjche.2020.11.009
    Abstract ( 28 )   PDF (466KB) ( 77 )  
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    Targeted therapy has been widely demonstrated as an effective strategy to treat cancers, the leading cause of death in the world. This minireview summarizes the technical platforms and methodologies utilized to develop and engineer therapeutic monoclonal antibodies and antibody-drug conjugates. First, the USA FDA approved monoclonal antibody (mAb)-based targeted therapies are reviewed. Then the representative innovative chimeric, humanized and fully human anti-cancer antibodies and antibody-drug conjugates are described. Finally, the past and predictive market trend of therapeutic antibodies is discussed.
    Molecular design, synthesis strategies and recent advances of hydrogels for wound dressing applications
    Dan Zeng, Shihong Shen, Daidi Fan
    2021, 29(2):  308-320.  doi:10.1016/j.cjche.2020.12.005
    Abstract ( 64 )   PDF (5875KB) ( 135 )  
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    With the changes in the modern disease spectrum, pressure ulcers, diabetic feet, and vascular-derived diseases caused refractory wounds is increasing rapidly. The development of wound dressings has partly improved the effect of wound management. However, traditional wound dressings can only cover the wound and block bacteria, but are generally powerless to recurrent wound infection and tissue healing. There is an urgent need to develop a new type of wound dressing with comprehensive performance to achieve multiple effects such as protecting the wound site from the external environment, absorbing wound exudate, anti-inflammatory, antibacterial, and accelerating wound healing process. Hydrogel wound dressings have the aforementioned characteristics, and can keep the wound in a moist environment because of the high water content, which is an ideal choice for wound treatment. This review introduces the wound healing process and the development and performance advantages of hydrogel wound dressings. The choice of different preparation materials gives the particularities of different hydrogel wound dressings. It also systematically explains the main physical and chemical crosslinking methods for hydrogel synthesis. Besides, in-depth discussion of four typical hydrogel wound dressings including double network hydrogels, nanocomposite hydrogels, drug-loaded hydrogels and smart hydrogels fully demonstrates the feasibility of developing hydrogels as wound dressing products and their future development trends.
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