生物设计研究(英文) Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0051

Shun-Cheng Liu, Longxing Xu, Yuejia Sun, Lijie Yuan, Hong Xu, Xiaoming Song, Liangdan Sun

引用次数: 0

Structural Bases of Dihydroxy Acid Dehydratase Inhibition and Biodesign for Self-Resistance. 二羟基酸脱氢酶抑制的结构基础和自我抗性的生物设计

生物设计研究(英文) Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0046

Xin Zang, Undramaa Bat-Erdene, Weixue Huang, Zhongshou Wu, Steve E Jacobsen, Yi Tang, Jiahai Zhou

{"title":"Structural Bases of Dihydroxy Acid Dehydratase Inhibition and Biodesign for Self-Resistance.","authors":"Xin Zang, Undramaa Bat-Erdene, Weixue Huang, Zhongshou Wu, Steve E Jacobsen, Yi Tang, Jiahai Zhou","doi":"10.34133/bdr.0046","DOIUrl":"10.34133/bdr.0046","url":null,"abstract":"Dihydroxy acid dehydratase (DHAD) is the third enzyme in the plant branched-chain amino acid biosynthetic pathway and the target for commercial herbicide development. We have previously reported the discovery of fungal natural product aspterric acid (AA) as a submicromolar inhibitor of DHAD through self-resistance gene directed genome mining. Here, we reveal the mechanism of AA inhibition on DHAD and the self-resistance mechanism of AstD, which is encoded by the self-resistance gene astD. As a competitive inhibitor, the hydroxycarboxylic acid group of AA mimics the binding of the natural substrate of DHAD, while the hydrophobic moiety of AA occupies the substrate entrance cavity. Compared to DHAD, AstD has a relatively narrow substrate channel to prevent AA from binding. Several mutants of DHAD were generated and assayed to validate the self-resistance mechanism and to confer Arabidopsis thaliana DHAD with AA resistance. These results will lead to the engineering of new type of herbicides targeting DHAD and provide direction for the ecological construction of herbicide-resistant crops.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"6 ","pages":"0046"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Next-Generation Tumor Targeting with Genetically Engineered Cell Membrane-Coated Nanoparticles. 利用基因工程细胞膜包裹的纳米粒子进行下一代肿瘤靶向治疗。

生物设计研究(英文) Pub Date : 2024-10-25 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0055

Quazi T H Shubhra, Xiaojun Cai, Qiang Cai

引用次数: 0

Microbial Cell Factories in the Bioeconomy Era: From Discovery to Creation. 生物经济时代的微生物细胞工厂：从发现到创造。

生物设计研究(英文) Pub Date : 2024-10-21 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0052

Xiongying Yan, Qiaoning He, Binan Geng, Shihui Yang

{"title":"Microbial Cell Factories in the Bioeconomy Era: From Discovery to Creation.","authors":"Xiongying Yan, Qiaoning He, Binan Geng, Shihui Yang","doi":"10.34133/bdr.0052","DOIUrl":"10.34133/bdr.0052","url":null,"abstract":"Microbial cell factories (MCFs) are extensively used to produce a wide array of bioproducts, such as bioenergy, biochemical, food, nutrients, and pharmaceuticals, and have been regarded as the \"chips\" of biomanufacturing that will fuel the emerging bioeconomy era. Biotechnology advances have led to the screening, investigation, and engineering of an increasing number of microorganisms as diverse MCFs, which are the workhorses of biomanufacturing and help develop the bioeconomy. This review briefly summarizes the progress and strategies in the development of robust and efficient MCFs for sustainable and economic biomanufacturing. First, a comprehensive understanding of microbial chassis cells, including accurate genome sequences and corresponding annotations; metabolic and regulatory networks governing substances, energy, physiology, and information; and their similarity and uniqueness compared with those of other microorganisms, is needed. Moreover, the development and application of effective and efficient tools is crucial for engineering both model and nonmodel microbial chassis cells into efficient MCFs, including the identification and characterization of biological parts, as well as the design, synthesis, assembly, editing, and regulation of genes, circuits, and pathways. This review also highlights the necessity of integrating automation and artificial intelligence (AI) with biotechnology to facilitate the development of future customized artificial synthetic MCFs to expedite the industrialization process of biomanufacturing and the bioeconomy.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"6 ","pages":"0052"},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unlocking the Potential of Collagenases: Structures, Functions, and Emerging Therapeutic Horizons. 释放胶原酶的潜能：释放胶原酶的潜力：结构、功能和新的治疗前景》（Unlock the Potential of Collagenases: Structures, Functions, and Emerging Therapeutic Horizons.

生物设计研究(英文) Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0050

Zhen-Zhen Wang, Kang Wang, Ling-Feng Xu, Chang Su, Jin-Song Gong, Jin-Song Shi, Xu-Dong Ma, Nan Xie, Jian-Ying Qian

{"title":"Unlocking the Potential of Collagenases: Structures, Functions, and Emerging Therapeutic Horizons.","authors":"Zhen-Zhen Wang, Kang Wang, Ling-Feng Xu, Chang Su, Jin-Song Gong, Jin-Song Shi, Xu-Dong Ma, Nan Xie, Jian-Ying Qian","doi":"10.34133/bdr.0050","DOIUrl":"https://doi.org/10.34133/bdr.0050","url":null,"abstract":"Collagenases, a class of enzymes that are specifically responsible for collagen degradation, have garnered substantial attention because of their pivotal roles in tissue repair, remodeling, and medical interventions. This comprehensive review investigates the diversity, structures, and mechanisms of collagenases and highlights their therapeutic potential. First, it provides an overview of the biochemical properties of collagen and highlights its importance in extracellular matrix function. Subsequently, it meticulously analyzes the sources of collagenases and their applications in tissue engineering and food processing. Notably, this review emphasizes the predominant role played by microbial collagenases in commercial settings while discussing their production and screening methods. Furthermore, this study elucidates the methodology employed for determining collagenase activity and underscores the importance of an accurate evaluation for both research purposes and clinical applications. Finally, this review highlights the future research prospects for collagenases, with a particular focus on promoting wound healing and treating scar tissue formation and fibrotic diseases.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"6 ","pages":"0050"},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic Gene Expression Mitigates Mutational Escape in Lysis-Driven Bacteria Cancer Therapy. 动态基因表达可减轻溶解驱动型细菌癌症疗法中的突变逃逸。

生物设计研究(英文) Pub Date : 2024-09-19 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0049

Filippo Liguori, Nicola Pellicciotta, Edoardo Milanetti, Sophia Xi Windemuth, Giancarlo Ruocco, Roberto Di Leonardo, Tal Danino

{"title":"Dynamic Gene Expression Mitigates Mutational Escape in Lysis-Driven Bacteria Cancer Therapy.","authors":"Filippo Liguori, Nicola Pellicciotta, Edoardo Milanetti, Sophia Xi Windemuth, Giancarlo Ruocco, Roberto Di Leonardo, Tal Danino","doi":"10.34133/bdr.0049","DOIUrl":"https://doi.org/10.34133/bdr.0049","url":null,"abstract":"Engineered bacteria have the potential to deliver therapeutic payloads directly to tumors, with synthetic biology enabling precise control over therapeutic release in space and time. However, it remains unclear how to optimize therapeutic bacteria for durable colonization and sustained payload release. Here, we characterize nonpathogenic Escherichia coli expressing the bacterial toxin Perfringolysin O (PFO) and dynamic strategies that optimize therapeutic efficacy. While PFO is known for its potent cancer cell cytotoxicity, we present experimental evidence that expression of PFO causes lysis of bacteria in both batch culture and microfluidic systems, facilitating its efficient release. However, prolonged expression of PFO leads to the emergence of a mutant population that limits therapeutic-releasing bacteria in a PFO expression level-dependent manner. We present sequencing data revealing the mutant takeover and employ molecular dynamics to confirm that the observed mutations inhibit the lysis efficiency of PFO. To analyze this further, we developed a mathematical model describing the evolution of therapeutic-releasing and mutant bacteria populations revealing trade-offs between therapeutic load delivered and fraction of mutants that arise. We demonstrate that a dynamic strategy employing short and repeated inductions of the pfo gene better preserves the original population of therapeutic bacteria by mitigating the effects of mutational escape. Altogether, we demonstrate how dynamic modulation of gene expression can address mutant takeovers giving rise to limitations in engineered bacteria for therapeutic applications.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"6 ","pages":"0049"},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biosynthesis of Diverse Ephedra-Type Alkaloids via a Newly Identified Enzymatic Cascade. 通过新发现的酶级联合成多种麻黄类生物碱

生物设计研究(英文) Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0048

Peiling Wu, Ding Luo, Yuezhou Wang, Xiaoxu Shang, Binju Wang, Xianming Deng, Jifeng Yuan

{"title":"Biosynthesis of Diverse Ephedra-Type Alkaloids via a Newly Identified Enzymatic Cascade.","authors":"Peiling Wu, Ding Luo, Yuezhou Wang, Xiaoxu Shang, Binju Wang, Xianming Deng, Jifeng Yuan","doi":"10.34133/bdr.0048","DOIUrl":"10.34133/bdr.0048","url":null,"abstract":"Ephedra-type alkaloids represent a large class of natural and synthetic phenylpropanolamine molecules with great pharmaceutical values. However, the existing methods typically rely on chemical approaches to diversify the N-group modification of Ephedra-type alkaloids. Herein, we report a 2-step enzymatic assembly line for creating structurally diverse Ephedra-type alkaloids to replace the conventional chemical modification steps. We first identified a new carboligase from Bacillus subtilis (BsAlsS, acetolactate synthase) as a robust catalyst to yield different phenylacetylcarbinol (PAC) analogs from diverse aromatic aldehydes with near 100% conversions. Subsequently, we screened imine reductases (IREDs) for the reductive amination of PAC analogs. It was found that IRG02 from Streptomyces albidoflavus had good activities with conversions ranging from 37% to 84% for the reductive alkylamination with diverse amine partners such as allylamine, propargylamine, and cyclopropylamine. Overall, 3 new bio-modifications at the N-group of Ephedra-type alkaloids were established. Taken together, our work lays a foundation for the future implementation of biocatalysis for synthesizing structurally diverse Ephedra-type alkaloids with potential new pharmaceutical applications.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"6 ","pages":"0048"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Subcellular Accumulation Design for Recombinant Protein Production in Tobacco. 烟草重组蛋白生产亚细胞积累设计的进展。

生物设计研究(英文) Pub Date : 2024-08-28 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0047

Shi-Jian Song, Hai-Ping Diao, Yong-Feng Guo, Inhwan Hwang

引用次数: 0

A Light-Driven In Vitro Enzymatic Biosystem for the Synthesis of α-Farnesene from Methanol. 从甲醇合成 α-法呢烯的光驱动体外酶促生物系统。

生物设计研究(英文) Pub Date : 2024-07-30 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0039

Xinyue Gui, Fei Li, Xinyu Cui, Ranran Wu, Dingyu Liu, Chunling Ma, Lijuan Ma, Huifeng Jiang, Chun You, Zhiguang Zhu

引用次数: 0

Lipid-Encapsulated Engineered Bacterial Living Materials Inhibit Cyclooxygenase II to Enhance Doxorubicin Toxicity. 脂质包裹的工程细菌活体材料可抑制环氧化酶 II，从而增强多柔比星的毒性。

生物设计研究(英文) Pub Date : 2024-06-25 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0038

Ning Jiang, Wanqing Ding, Xiaojuan Zhu, Jianshu Chen, Lin Yang, Xiaoping Yi, Yingping Zhuang, Jiangchao Qian, Jiaofang Huang

{"title":"Lipid-Encapsulated Engineered Bacterial Living Materials Inhibit Cyclooxygenase II to Enhance Doxorubicin Toxicity.","authors":"Ning Jiang, Wanqing Ding, Xiaojuan Zhu, Jianshu Chen, Lin Yang, Xiaoping Yi, Yingping Zhuang, Jiangchao Qian, Jiaofang Huang","doi":"10.34133/bdr.0038","DOIUrl":"10.34133/bdr.0038","url":null,"abstract":"Recently, there has been increasing interest in the use of bacteria for cancer therapy due to their ability to selectively target tumor sites and inhibit tumor growth. However, the complexity of the interaction between bacteria and tumor cells evokes unpredictable therapeutic risk, which induces inflammation, stimulates the up-regulation of cyclooxygenase II (COX-2) protein, and stimulates downstream antiapoptotic gene expression in the tumor microenvironment to reduce the antitumor efficacy of chemotherapy and immunotherapy. In this study, we encapsulated celecoxib (CXB), a specific COX-2 inhibitor, in liposomes anchored to the surface of Escherichia coli Nissle 1917 (ECN) through electrostatic absorption (C@ECN) to suppress ECN-induced COX-2 up-regulation and enhance the synergistic antitumor effect of doxorubicin (DOX). C@ECN improved the antitumor effect of DOX by restraining COX-2 expression. In addition, local T lymphocyte infiltration was induced by the ECN to enhance immunotherapy efficacy in the tumor microenvironment. Considering the biosafety of C@ECN, a hypoxia-induced lysis circuit, pGEX-Pvhb-Lysis, was introduced into the ECN to limit the number of ECNs in vivo. Our results indicate that this system has the potential to enhance the synergistic effect of ECN with chemical drugs to inhibit tumor progression in medical oncology.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"6 ","pages":"0038"},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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