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":null,"pages":null},"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":null,"pages":null},"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

Copper-Induced In Vivo Gene Amplification in Budding Yeast. 铜诱导芽殖酵母体内基因扩增。

生物设计研究(英文) Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0030

Junyi Wang, Jingya Song, Cong Fan, Jiahao Duan, Kaiyuan He, Jifeng Yuan

{"title":"Copper-Induced In Vivo Gene Amplification in Budding Yeast.","authors":"Junyi Wang, Jingya Song, Cong Fan, Jiahao Duan, Kaiyuan He, Jifeng Yuan","doi":"10.34133/bdr.0030","DOIUrl":"10.34133/bdr.0030","url":null,"abstract":"In the biotechnological industry, multicopy gene integration represents an effective strategy to maintain a high-level production of recombinant proteins and to assemble multigene biochemical pathways. In this study, we developed copper-induced in vivo gene amplification in budding yeast for multicopy gene expressions. To make copper as an effective selection pressure, we first constructed a copper-sensitive yeast strain by deleting the CUP1 gene encoding a small metallothionein-like protein for copper resistance. Subsequently, the reporter gene fused with a proline-glutamate-serine-threonine-destabilized CUP1 was integrated at the δ sites of retrotransposon (Ty) elements to counter the copper toxicity at 100 μM Cu2+. We further demonstrated the feasibility of modulating chromosomal rearrangements for increased protein expression under higher copper concentrations. In addition, we also demonstrated a simplified design of integrating the expression cassette at the CUP1 locus to achieve tandem duplication under high concentrations of copper. Taken together, we envision that this method of copper-induced in vivo gene amplification would serve as a robust and useful method for protein overproduction and metabolic engineering applications in budding yeast.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10976586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320015","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 the Application of Single-Cell Transcriptomics in Plant Systems and Synthetic Biology. 单细胞转录组学在植物系统和合成生物学中的应用进展。

生物设计研究(英文) Pub Date : 2024-02-29 eCollection Date: 2024-01-01 DOI: 10.34133/bdr.0029

Md Torikul Islam, Yang Liu, Md Mahmudul Hassan, Paul E Abraham, Jean Merlet, Alice Townsend, Daniel Jacobson, C Robin Buell, Gerald A Tuskan, Xiaohan Yang

{"title":"Advances in the Application of Single-Cell Transcriptomics in Plant Systems and Synthetic Biology.","authors":"Md Torikul Islam, Yang Liu, Md Mahmudul Hassan, Paul E Abraham, Jean Merlet, Alice Townsend, Daniel Jacobson, C Robin Buell, Gerald A Tuskan, Xiaohan Yang","doi":"10.34133/bdr.0029","DOIUrl":"10.34133/bdr.0029","url":null,"abstract":"Plants are complex systems hierarchically organized and composed of various cell types. To understand the molecular underpinnings of complex plant systems, single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for revealing high resolution of gene expression patterns at the cellular level and investigating the cell-type heterogeneity. Furthermore, scRNA-seq analysis of plant biosystems has great potential for generating new knowledge to inform plant biosystems design and synthetic biology, which aims to modify plants genetically/epigenetically through genome editing, engineering, or re-writing based on rational design for increasing crop yield and quality, promoting the bioeconomy and enhancing environmental sustainability. In particular, data from scRNA-seq studies can be utilized to facilitate the development of high-precision Build-Design-Test-Learn capabilities for maximizing the targeted performance of engineered plant biosystems while minimizing unintended side effects. To date, scRNA-seq has been demonstrated in a limited number of plant species, including model plants (e.g., Arabidopsis thaliana), agricultural crops (e.g., Oryza sativa), and bioenergy crops (e.g., Populus spp.). It is expected that future technical advancements will reduce the cost of scRNA-seq and consequently accelerate the application of this emerging technology in plants. In this review, we summarize current technical advancements in plant scRNA-seq, including sample preparation, sequencing, and data analysis, to provide guidance on how to choose the appropriate scRNA-seq methods for different types of plant samples. We then highlight various applications of scRNA-seq in both plant systems biology and plant synthetic biology research. Finally, we discuss the challenges and opportunities for the application of scRNA-seq in plants.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023395","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

Ice Cores as a Source for Antimicrobials: From Bioprospecting to Biodesign. 冰芯作为抗菌药物的来源：从生物勘探到生物设计。

生物设计研究(英文) Pub Date : 2023-11-02 eCollection Date: 2023-01-01 DOI: 10.34133/bdr.0024

Ying-Chiang Jeffrey Lee, Bahar Javdan

{"title":"Ice Cores as a Source for Antimicrobials: From Bioprospecting to Biodesign.","authors":"Ying-Chiang Jeffrey Lee, Bahar Javdan","doi":"10.34133/bdr.0024","DOIUrl":"https://doi.org/10.34133/bdr.0024","url":null,"abstract":"The golden age has passed for antibiotic discovery, and while some antibiotics are currently in various phases of clinical trials in the United States, many pharmaceutical companies have abandoned antibiotic research. With the need for antibiotics, we should expand our horizon for therapeutic mining and can look toward understudied sources such as ice cores. Ice cores contain microorganisms and genetic material that have been frozen in time for thousands of years. The antibiotics used by these organisms are encoded in their genomes, which can be unlocked, identified, and characterized with modern advances in molecular biology, genetic sequencing, various computational approaches, and established natural product discovery pipelines. While synthetic biology can be used in natural product discovery approaches, synthetic biology and bioengineering efforts can also be leveraged in the selection and biodesign of increased compound yields, potency, and stability. Here, we provide the perspective that ice cores can be a source of novel antibiotic compounds and that the tools of synthetic biology can be used to design better antimicrobials.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489482","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

Design and Construction of Artificial Biological Systems for One-Carbon Utilization. 一碳利用人工生物系统的设计与构建。

生物设计研究(英文) Pub Date : 2023-10-31 eCollection Date: 2023-01-01 DOI: 10.34133/bdr.0021

Wei Zhong, Hailong Li, Yajie Wang

{"title":"Design and Construction of Artificial Biological Systems for One-Carbon Utilization.","authors":"Wei Zhong, Hailong Li, Yajie Wang","doi":"10.34133/bdr.0021","DOIUrl":"https://doi.org/10.34133/bdr.0021","url":null,"abstract":"The third-generation (3G) biorefinery aims to use microbial cell factories or enzymatic systems to synthesize value-added chemicals from one-carbon (C1) sources, such as CO2, formate, and methanol, fueled by renewable energies like light and electricity. This promising technology represents an important step toward sustainable development, which can help address some of the most pressing environmental challenges faced by modern society. However, to establish processes competitive with the petroleum industry, it is crucial to determine the most viable pathways for C1 utilization and productivity and yield of the target products. In this review, we discuss the progresses that have been made in constructing artificial biological systems for 3G biorefineries in the last 10 years. Specifically, we highlight the representative works on the engineering of artificial autotrophic microorganisms, tandem enzymatic systems, and chemo-bio hybrid systems for C1 utilization. We also prospect the revolutionary impact of these developments on biotechnology. By harnessing the power of 3G biorefinery, scientists are establishing a new frontier that could potentially revolutionize our approach to industrial production and pave the way for a more sustainable future.","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429606","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

Towards Plant Synthetic Genomics. 走向植物合成基因组学。

生物设计研究(英文) Pub Date : 2023-10-16 eCollection Date: 2023-01-01 DOI: 10.34133/bdr.0020

Yuling Jiao, Ying Wang

引用次数: 0

CRISPR-Cas-Based Engineering of Probiotics. 基于CRISPR-Cas的益生菌工程。

生物设计研究(英文) Pub Date : 2023-09-29 eCollection Date: 2023-01-01 DOI: 10.34133/bdr.0017

Ling Liu, Shimaa Elsayed Helal, Nan Peng

引用次数: 1

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