Structural basis and mechanism of SAM-utilizing PLP-dependent enzymes

利用 SAM 的 PLP 依赖性酶的结构基础和机制

• 批准号: 530632985
• 负责人: Professorin Dr. Lena Barra
• 金额: --
• 依托单位: AG Biologische Chemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/530632985?language=en
• 关键词: Structural; basis; mechanism; SAM; utilizing

S-adenosylmethionine (SAM)-utilizing pyridoxal phosphate (PLP)-dependent enzymes (SAM-PLP enzymes) are an emerging family of biocatalysts that stand out in terms of their remarkable chemical versatility rooted in the combined and potentiated reactivities of the carbanion-stabilizing cofactor PLP and the multifunctional nature of the sulfonium-bearing SAM. Reported enzyme-mediated transformations range from intramolecular cyclopropylations, to intermolecular Claisen-like reactions, C-N bond-forming aza-Michael-type additions, or tandem C-C bond formations via (3+2)-cycloaddition. The steadily increasing number of available genomic and metagenomic data represents a vast resource for the discovery of novel biocatalysts by targeted data mining. However, due to the current lack of in-depth structural and mechanistic knowledge for SAM-PLP enzymes, no methods are available for functional annotation based on sequence data. The goal of the project is to elucidate key structural and mechanistic determinants for SAM binding and conversion by SAM-PLP enzymes and the subsequent development of bioinformatic tools for targeted enzyme discovery approaches by genomic data mining. The results will provide a deeper understanding of the enzymological and evolutionary functions of SAM and will lay the basis to explore and exploit the versatile group of SAM-PLP biocatalysts.

利用S-腺苷甲硫氨酸（SAM）的磷酸吡哆醛（PLP）依赖性酶（SAM-PLP酶）是一种新兴的生物催化剂家族，其突出之处在于其显著的化学多功能性，其植根于碳负离子稳定辅因子PLP的组合和增强的反应性以及携带锍的SAM的多功能性质。报道的酶介导的转化范围从分子内环丙基化，分子间克莱森样反应，C-N键形成氮杂迈克尔型加成，或串联C-C键形成通过（3+2）-环加成。稳定增加的可用基因组和宏基因组数据的数量代表了通过有针对性的数据挖掘发现新型生物催化剂的巨大资源。然而，由于目前缺乏对SAM-PLP酶的深入的结构和机制知识，没有方法可用于基于序列数据的功能注释。该项目的目标是阐明SAM结合和转化的关键结构和机制决定因素SAM-PLP酶和生物信息学工具的后续发展有针对性的酶发现方法的基因组数据挖掘。本研究结果将为深入了解SAM的酶学和进化功能提供理论依据，并为探索和开发多功能SAM PLP生物催化剂奠定基础。