Understanding the Iterative Polyketide Synthase Involved in Fungal Strobilurin Biosynthesis

了解真菌甲氧基丙烯酸酯生物合成中涉及的迭代聚酮合酶

• 批准号: 448357958
• 负责人: Professor Dr. Russell J. Cox
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/448357958?language=en
• 关键词: Understanding; Iterative; Polyketide; Synthase; Involved

Strobilurins are fungal metabolites which are produced by an unusual interative polyketide synthase (iPKS) which creates an unprecedented E,Z,E triene. Understanding the function and programming of iPKS is important because these enzymes could be reprogrammed to make sustainable compound synthesis platforms in future. The strobilurin iPKS presents a perplexing problem: how does a single dehydratase enzyme provide a different geometry of olefin in each beta-processing cycle? In addition, the system also specifies a very unusual benzoate starter unit. The strobilurin iPKS should provide very useful information about how to engineer other iPKS to have different starter units and different olefin geometries. The project will involve the expression and production of individual catalytic domains of the strobilurin iPKS and synthesis of small-molecule substrates. This will allow in vitro assays to be developed which will facilitate the study of the selectivity and mechanisms of the acy transferase and dehydratase catalytic domains. The Strobilurin iPKS also contains very unusual C-terminal catalytic domains, including an 'extra' C-methyltransferase, a fragment of a thiolesterase and a domain of unknown function. We will also study how these domains interact with and process chemical intermediates during the biosynthesis of the strobilurin polyketide.

嗜球果伞素是真菌代谢产物，其由不寻常的交互式聚酮合酶（iPKS）产生，所述iPKS产生前所未有的E，Z，E三烯。了解iPKS的功能和编程是很重要的，因为这些酶可以重新编程，以使未来的可持续化合物合成平台。嗜球果伞素iPKS提出了一个令人困惑的问题：单一的β-淀粉酶如何在每个β-加工循环中提供不同几何形状的烯烃？此外，该系统还指定了一个非常不寻常的苯甲酸酯起始单元。嗜球果伞素iPKS应提供关于如何工程化其它iPKS以具有不同起始单元和不同烯烃几何形状的非常有用的信息。该项目将涉及嗜球果伞素iPKS的单个催化结构域的表达和生产以及小分子底物的合成。这将允许开发体外测定法，其将促进酰基转移酶和乙酰氨基转移酶催化结构域的选择性和机制的研究。Strobilurin iPKS还含有非常不寻常的C-末端催化结构域，包括一个“额外的”C-甲基转移酶，一个硫酯酶片段和一个未知功能的结构域。我们还将研究这些结构域如何在嗜球果伞素聚酮的生物合成过程中与化学中间体相互作用和加工。