CAREER: Mechanism of Cytochrome P450 Alkene Biosynthesis

职业：细胞色素P450烯烃生物合成的机制有了这个CAREER奖，NSF化学部的生命过程化学正在资助南卡罗来纳州大学的托马斯Makris博士研究OleT的机制，OleT是一种最近发现的参与碳氢化合物合成的酶。 生物催化生产碳氢化合物为可持续地生产与现有能源基础设施兼容的燃料提供了一条潜在途径。 OleT催化的非典型反应消耗过氧化氢，一种有毒的活性氧，并将生物丰富的脂肪酸转化为烯烃，而无需任何额外的能量输入。 这项研究的目标是了解这一反应的化学过程，以及促进它的分子细节。这项研究的其他更广泛的影响是本科生和高中生以及整个社区的积极参与，正在进行的蛋白质工程计划将这种碳氢化合物生产能力引入相关酶。 该奖项还通过与女子文理学院的合作交流，支持国内机构和国外的本科生的研究，并为来自代表性不足的少数民族的高中生提供第一个研究机会。细胞色素P450是一个普遍表达的巯基连接血红素酶超家族，催化各种生理上重要的化学反应。 细胞色素P450酶通常使用称为化合物I的铁基中间体将氧原子插入有机底物中。 OleT形成化合物I，但催化一个根本不同的反应，不涉及氧插入。 这种不寻常的金属氧重编程的起源正在通过生物化学，动力学，光谱和结构方法进行探索。 这些方法评估个人的贡献，电子结构，二级配位领域，和基板定位上促进碳-碳断裂反应。 Makris博士设计了一个创新的教育计划，称为脂肪燃料，这是很好地融入OleT的拟议研究。 在这个计划中，本科生和当地社区正在学习如何将脂肪转化为碳氢化合物燃料。这项研究有可能在开发新的碳氢化合物来源作为化石燃料的替代品方面影响社会。

CAREER: Mechanism of Cytochrome P450 Alkene BiosynthesisWith this CAREER award, the Chemistry of Life Processes in the Chemistry Division of NSF is funding Dr. Thomas Makris from the University of South Carolina to study the mechanism of OleT, a recently discovered enzyme that is involved in the synthesis of hydrocarbons. The biocatalytic production of hydrocarbons provides a potential route to sustainably produce fuels that are compatible within the existing energy infrastructure. The atypical reaction catalyzed by OleT consumes hydrogen peroxide, a toxic reactive oxygen species, and transforms biologically abundant fatty acids into alkenes without any additional input of energy. The goal of this research is to understand both the chemistry of this reaction, and the molecular details which promote it. Additional broader impacts of this research are in its active involvement of undergraduate and high school students, and the community at large, in an ongoing protein engineering initiative that introduces this hydrocarbon producing capacity into a related enzyme. The award also supports research for undergraduates from the home institution, and abroad, through a collaborative exchange with a liberal arts college for women, and provides the first research opportunities to high-school students from underrepresented minorities.The cytochromes P450 are a ubiquitously expressed superfamily of thiolate-ligated heme enzymes that catalyze a diverse set of physiologically important chemical reactions. Cytochrome P450 enzymes typically insert oxygen atoms into organic substrates using a ferryl intermediate known as Compound I. OleT forms Compound I, but instead catalyzes a fundamentally different reaction that does not involve oxygen insertion. The origins for this unusual metal-oxo reprogramming are being probed by biochemical, kinetics, spectroscopic and structural methods. These methodologies evaluate the individual contributions of electronic structure, secondary coordination sphere, and substrate positioning on promoting the carbon-carbon scission reaction. Dr. Makris has devised an innovative educational plan, termed Fats to Fuels, that is well integrated into the proposed studies of OleT. In this plan, undergraduate students and the local community are engaged in learning how fats can be converted to hydrocarbon fuel sources. This research has the potential to impact society with respect to developing new hydrocarbon sources as alternatives to fossil fuels.