Molecular and structural biology of phycocyanobilin:ferredoxin oxidoreductases

智力优势：植物胆磷脂是一种色素，在从单细胞藻类到绿色植物的氧光合生物中起着重要的光收集作用。当附着在蛋白质（胆囊蛋白）上时，植物胆囊素收集光能，驱动蓝绿、红和褐藻的光合作用，并触发对在不断波动的光环境中生存至关重要的适应性信号通路。这个项目的重点是铁氧化还蛋白依赖的胆磷脂还原酶（FDBRs），这是一个金属自由基酶家族，负责两类光传感器蛋白的植物胆磷脂色素前体的合成。本研究利用多种生物化学和生物物理技术，通过x射线晶体学、分子生物学和生物化学分析的结合，试图在分子水平上阐明FDBR的功能。这些知识对于开发FDBRs的活化剂/抑制剂是必需的，这些活化剂/抑制剂可用于增强地球上所有生命所依赖的氧气进化光合生物的光感知、生长和发育。这些研究还试图了解一种独特的FDBR基因在绿藻莱茵衣藻中的生物学作用，衣藻是一种缺氧光合生物，缺乏所有已知的光感胆蛋白。通过对该生物的遗传、基因组和表型分析，将对该基因功能的几种假设进行评估。预计这些研究将导致对迄今未被认识到的十亿蛋白代谢的新功能的深入了解。由于衣藻保留了植物和动物共同的特征，这项研究不仅有望为提高作物生产力提供新的途径，而且可能揭示与人类/动物生理和疾病相关的新的十亿蛋白依赖调控途径。该研究项目的广泛影响将通过培养分子生物学、酶学、蛋白质化学、结构生物学、计算生物学和反向遗传学方法的各级科学家（博士后、研究生、本科生和高中生），将研究和教育结合起来。本科生（包括代表性不足的少数民族学生）将进行这项研究的许多方面。此外，为了扩大弱势群体的参与并促进教学，实验室参与了一系列发展和少数群体培训项目，包括：MURPPS（少数族裔本科生参与物理科学研究项目）、SURPRISE（科学与工程暑期本科生研究项目）、BUSP（生物学本科生研究项目），以及包括青年学者项目、SEED（通过卓越和多样性项目在工程领域取得成功）和戴维斯高中高级生物技术课程在内的高中项目。该项目得到了MCB生物分子系统集群和CHE无机、生物无机和有机金属化学项目的支持。

Intellectual merit: Phytobilins are pigments that perform significant light harvesting roles in oxygenic photosynthetic organisms from unicellular algae to green plants. When attached to proteins (biliproteins), phytobilins harvest light energy to drive photosynthesis in blue-green, red and brown algae, and trigger adaptive signaling pathways vital to survival in a constantly fluctuating light environment. This project focuses on ferredoxin-dependent bilin reductases (FDBRs), a family of metal-free radical enzymes that are responsible for the synthesis of phytobilin pigment precursors of both classes of light sensor proteins. Using a variety of biochemical and biophysical techniques, this research seeks to elucidate FDBR function at the molecular level via a combination of x-ray crystallography, molecular biology and biochemical analysis. Such knowledge is needed for development of activators/inhibitors of FDBRs that can be used to enhance light perception, growth and development of oxygen-evolving photosynthetic organisms upon which all life on earth depends. These studies also seek to understand the biological role of a unique FDBR gene in the green alga Chlamydomonas reinhardtii, an oxygenic photosynthetic organism that lacks all known light sensing biliproteins. Using genetic, genomic and phenotypic analyses of this organism, several hypotheses for the function of this gene will be assessed. It is anticipated that such studies will lead to insight into new functions of bilin metabolism hitherto unrecognized. Since Chlamydomonas retains features common to plants and animals, this research is expected not only to yield new avenues to improve crop productivity, but could reveal novel bilin-dependent regulatory pathways of relevance to human/animal physiology and disease. The broader impact of this research project will integrate research and education by training scientists at all levels (postdocs, graduate, undergraduate and high school students) in the methods of molecular biology, enzymology, protein chemistry, structural biology, computational biology and reverse genetics. Undergraduates (including an underrepresented minority student) will conduct a number of aspects of this research. Additionally, to broaden participation of underrepresented groups and pto romote teaching, the labs participate in a number of development and minority-training programs, including: MURPPS (Minority Undergraduate Research Participation in the Physical Sciences), SURPRISE (Summer Undergraduate Research Program In Science and Engineering), BUSP (Biology Undergraduate Scholars Program), and in high school programs including Young Scholar Program, SEED (Success in Engineering through Excellence and Diversity Program), and Davis high school advanced biotechnology class.This project is being supported by the Biomolecular Systems cluster in MCB and the Inorganic, Bioinorganic, and Organometallic Chemistry program in CHE.