Deciphering the substrate specificity code of basidiomycete peptide synthetases
破译担子菌肽合成酶的底物特异性代码
基本信息
- 批准号:242358822
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2013
- 资助国家:德国
- 起止时间:2012-12-31 至 2016-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The number of fully sequenced and publically accessible basidiomycete genomes is increasing at a fast pace. It has become evident that many species within this diverse group of fungi harbor the genetic material for a structurally diverse secondary metabolism to biosynthesize small molecule natural products, the majority of which has not been identified and chemically characterized yet. This research project serves to close this gap between genomics and natural product chemistry by enabling the prediction of natural product (partial) structures from genomic sequence data. The objective is to identify and characterize secondary metabolomes in a more straightforward way. Hence, discovery of new bioactive compounds which may serve as pharmaceutically relevant drug leads is facilitated.This work combines biochemistry, bioinformatics, and natural product chemistry, and focuses on nonribosomal peptide synthetases (NRPSs) and related proteins. These are multidomain enzymes which catalyze the assembly of complex natural products from generic substrates, such as amino acids, keto acids, and others. The substrate specificity and, thus, structural features of the product, is governed by ten positions within the primary NRPS amino acid sequence, which are collectively referred to as NRPS-code. This code is virtually unknown for the basidiomycetes.In vitro biochemical characterization of peptide synthetases of select Basidiomycota species will profile the substrate specificities and establish an NRPS-code for the individual substrates. This approach is supported by modeling the respective enzymes/domains in silico. Chemical investigations with the chosen fungal species, primarily feeding of labeled substrates, and natural product isolation and structure elucidation, will verify biochemical results.
已完全测序并可通过化学方法获得的担子菌基因组的数量正在快速增加。很明显,这一不同真菌群中的许多物种具有用于结构多样的次级代谢的遗传物质,以生物合成小分子天然产物,其中大部分尚未被鉴定和化学表征。该研究项目旨在通过从基因组序列数据预测天然产物(部分)结构来缩小基因组学和天然产物化学之间的差距。目的是以更直接的方式鉴定和表征次级代谢组。本论文结合生物化学、生物信息学和天然产物化学,重点研究非核糖体肽合成酶(NRPSs)及其相关蛋白质。这些是多结构域酶,其催化从通用底物(例如氨基酸、酮酸等)组装复杂的天然产物。底物特异性以及产物的结构特征由一级NRPS氨基酸序列内的10个位置控制,这些位置统称为NRPS密码。这个代码是几乎未知的basidiomycetes.In体外生物化学特性的肽合成酶的选择Basidiomycota物种将配置文件的底物特异性,并建立一个NRPS代码的个别基板。这种方法通过计算机模拟相应的酶/结构域来支持。化学调查与选定的真菌物种,主要喂养标记的基板,天然产物的分离和结构阐明,将验证生化结果。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A Highly Conserved Basidiomycete Peptide Synthetase Produces a Trimeric Hydroxamate Siderophore
- DOI:10.1128/aem.01478-17
- 发表时间:2017-11-01
- 期刊:
- 影响因子:4.4
- 作者:Brandenburger, Eileen;Gressler, Markus;Hoffmeister, Dirk
- 通讯作者:Hoffmeister, Dirk
Functional and Phylogenetic Divergence of Fungal Adenylate-Forming Reductases
- DOI:10.1128/aem.01767-14
- 发表时间:2014-10-01
- 期刊:
- 影响因子:4.4
- 作者:Kalb, Daniel;Lackner, Gerald;Hoffmeister, Dirk
- 通讯作者:Hoffmeister, Dirk
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Professor Dr. Dirk Hoffmeister其他文献
Professor Dr. Dirk Hoffmeister的其他文献
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{{ truncateString('Professor Dr. Dirk Hoffmeister', 18)}}的其他基金
Biochemical and genetic basis of oligocyclic aromatic polyketide formation in basidiomycetes
担子菌中寡环芳香族聚酮化合物形成的生化和遗传基础
- 批准号:
413891605 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Research Grants
Biochemical and genetic basis of indole alkaloid formation in the basidiomycete Psilocybe cyanescens
担子菌裸盖菌中吲哚生物碱形成的生化和遗传基础
- 批准号:
318716222 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Grants
Untersuchungen zur Naturstoffbiosynthese und -modifikation im Phytopathogen Ralstonia solanacearum
植物病原菌青枯菌天然产物生物合成及修饰研究
- 批准号:
217074385 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
Untersuchungen zur funktionellen Diversität von Chinonsynthetase-ähnlichen Enzymen aus Basidiomyceten
担子菌类醌合成酶功能多样性的研究
- 批准号:
165159796 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Research Grants
Creation of improved galactokinases for natural product glycorandomization
创建用于天然产物糖随机化的改良半乳激酶
- 批准号:
5396818 - 财政年份:2002
- 资助金额:
-- - 项目类别:
Research Fellowships
The structural basis of psilocybin biosynthesis
裸盖菇素生物合成的结构基础
- 批准号:
456463463 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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