Investigating multi-functional cytochromes P450 from gibberellin phytohormone biosynthesis

研究赤霉素植物激素生物合成中的多功能细胞色素 P450

• 批准号: 1609917
• 负责人: Reuben Peters
• 金额: $ 32.89万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1609917&HistoricalAwards=false
• 关键词: Investigating; multi; functional; cytochromes; P450

With this award, the Chemistry of Life Processes Program in the Chemistry Division of NSF is funding Dr. Reuben Peters from Iowa State University for studies into how certain enzymes catalyze the production of natural products. These natural products have a variety of industrial uses, including as flavors and fragrances. Key roles in the production of these compounds are played by enzymes which typically simply insert an atom of oxygen, but are now known to be capable of much more complex chemical transformations. Several such multi-functional enzymes have been identified in the biosynthetic pathway leading to production of an important plant hormone and these will be studied in detail in this project. The researchers are elucidating how these enzymes accomplish their chemical reactions. The project has clear biotechnological relevance, as one of the enzymes targeted has already drawn interest for use in the production of natural sweeteners. Additionally the graduate and undergraduate students participating in this work are gaining expertise in cutting-edge studies of enzymes with industrial relevance. Finally the inclusion of high-school science teachers extends the reach of this project to the K-12 community. This project investigates cytochromes P450 (CYPs), which are heme-thiolate mono-oxygenases that generally catalyze hydroxylation, but are capable of much more complex reactions. This can be seen in biosynthesis of gibberellin (GA), a phytohormone whose effect on plant-microbe interactions has led to the independent evolution of GA biosynthesis in plant-associated microbes, including bacteria, from which the relevant multi-functional CYPs have been recently identified. These soluble enzymes are amendable to more detailed investigations. Through these studies, the reaction mechanisms and enzymatic structure-function relationships of the multi-functional CYPs from bacterial GA biosynthesis are being elucidated, furthering understanding of how the basic CYP catalytic cycle is modified to accomplish more complex/unusual reactions, which is currently one of the outstanding questions in enzymology/bioinorganic chemistry, with clear biotechnological implications.

有了这个奖项，美国国家科学基金会化学部的生命过程化学项目正在资助来自爱荷华州州立大学的鲁本·彼得斯博士研究某些酶如何催化天然产物的生产。这些天然产物具有多种工业用途，包括作为调味剂和香料。 在这些化合物的生产中起关键作用的是酶，这些酶通常只是插入一个氧原子，但现在已知能够进行更复杂的化学转化。在生物合成途径中已经鉴定了几种这样的多功能酶，导致产生一种重要的植物激素，本项目将对这些酶进行详细研究。研究人员正在阐明这些酶是如何完成化学反应的。该项目具有明显的生物技术相关性，因为目标酶之一已经引起了用于生产天然甜味剂的兴趣。 此外，参与这项工作的研究生和本科生正在获得与工业相关的酶的前沿研究的专业知识。 最后，高中科学教师的参与将该项目的范围扩大到K-12社区。该项目研究细胞色素P450（CYP），这是血红素硫醇单加氧酶，通常催化羟基化，但能够进行更复杂的反应。 这可以在赤霉素（GA）的生物合成中看到，赤霉素是一种植物激素，其对植物-微生物相互作用的影响已经导致GA生物合成在植物相关微生物（包括细菌）中的独立进化，最近已经从细菌中鉴定出相关的多功能CYP。 这些可溶性酶可用于更详细的研究。 通过这些研究，阐明了细菌GA生物合成的多功能CYP的反应机制和酶的结构-功能关系，进一步理解了基本的酶催化循环如何被修改以完成更复杂/不寻常的反应，这是目前酶学/生物无机化学中的突出问题之一，具有明确的生物技术意义。