Discovery and mechanisms of biosynthetic enzymes

生物合成酶的发现及其机制

• 批准号: 10623071
• 负责人: VAHE BANDARIAN
• 金额: $ 60.17万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10623071
• 关键词: Anabolism; Biochemical; Biological; Clinic; Complex; Development; Disease; Environment; Enzymes; Glean; Goals; Metabolism; Molecular; Natural Products; Nucleic Acids; Organism; Pathway interactions; Peptides; Physiology; Process; Ribosomes; Role; Structure-Activity Relationship; Techniques; enzyme mechanism; insight; novel; secondary metabolite; small molecule; therapeutic development

PROJECT SUMMARY Biosynthetic pathways are rich in enzymatic transformations that produce structurally diverse natural products, such as secondary metabolites, modified nucleic acids, and modified peptides. Discovering and understanding the molecular basis for these transformations underpins efforts towards development of deep insights into factors that either belie many disease processes, or their use in development of therapeutic agents. The focus of the proposed studies will be elucidating the mechanisms of enzymes that employ radical transformations in effecting complex transformation in the biosynthesis of ribosomally produced and posttranslationally modified peptides. This application will make use of biochemical, structural, and spectroscopic techniques to probe the mechanisms of these enzymes, establish structure-function relationships, and to discover novel biosynthetic enzymes.

项目摘要 生物合成途径富含酶促转化， 多种天然产物，如次级代谢产物、修饰的核酸，以及 修饰肽。发现和理解这些的分子基础 变革是努力深入了解各种因素的基础， 或者掩盖许多疾病过程，或者它们在治疗剂开发中的用途。 拟议研究的重点将是阐明酶的机制， 在生物合成中使用自由基转化来实现复杂的转化， 核糖体产生的和后修饰的肽。此应用程序将 利用生物化学，结构和光谱技术来探测 这些酶的机制，建立结构-功能关系，并发现 新的生物合成酶。

项目成果

Pathways of thymidine hypermodification.

• DOI: 10.1093/nar/gkab781
• 发表时间: 2022-04-08
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Lee YJ;Dai N;Müller SI;Guan C;Parker MJ;Fraser ME;Walsh SE;Sridar J;Mulholland A;Nayak K;Sun Z;Lin YC;Comb DG;Marks K;Gonzalez R;Dowling DP;Bandarian V;Saleh L;Corrêa IR;Weigele PR
• 通讯作者: Weigele PR

Analysis of Electrochemical Properties of S-Adenosyl-l-methionine and Implications for Its Role in Radical SAM Enzymes.

S-腺苷-L-甲硫氨酸的电化学性质分析及其在自由基 SAM 酶中的作用的意义。

• DOI: 10.1021/jacs.9b00933
• 发表时间: 2019
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Miller,SvenA;Bandarian,Vahe
• 通讯作者: Bandarian,Vahe

Leveraging Substrate Promiscuity of a Radical S-Adenosyl-L-methionine RiPP Maturase toward Intramolecular Peptide Cross-Linking Applications.

利用自由基 S-腺苷-L-甲硫氨酸 RiPP 成熟酶的底物混杂性进行分子内肽交联应用。

• DOI: 10.1021/acscentsci.2c00501
• 发表时间: 2022-08-24
• 期刊: ACS CENTRAL SCIENCE
• 影响因子: 18.2
• 作者: Eastman, Karsten A. S.;Kincannon, William M.;Bandarian, Vahe
• 通讯作者: Bandarian, Vahe

Insertion of 4-Demethylwyosine in tRNAPhe Catalyzed by the Radical S-Adenosyl-l-methionine Enzyme TYW1 Entails Oxidative Cleavage of Pyruvate to Form CO2.

在自由基 S-腺苷-l-甲硫氨酸酶 TYW1 的催化下，在 tRNAPhe 中插入 4-去甲基维索氨酸会导致丙酮酸氧化裂解形成 CO2。

• DOI: 10.1021/acs.biochem.2c00519
• 发表时间: 2022
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Young,AnthonyP;Bandarian,Vahe
• 通讯作者: Bandarian,Vahe

Eukaryotic TYW1 Is a Radical SAM Flavoenzyme.

• DOI: 10.1021/acs.biochem.1c00349
• 发表时间: 2021-07-13
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Young AP;Bandarian V
• 通讯作者: Bandarian V