Artificial metalloproteins: photochemical and electrochemical approaches for understanding mechanism and catalysis

气候变化的加速要求开发新技术，使人们能够获得可再生的化学燃料和原料。尽管目前研究了许多方法，但利用蛋白质催化仍然是一种未实现的资源，特别是对于氧化还原转化（例如，二氧化碳到甲醇）。氧化还原酶是催化的理想候选者，因为它们自然地对复杂转化所需的高能电子施加精细的控制。我们对多步电子转移反应和蛋白质设计的理解的最新进展，为研究人工修饰的蛋白质催化剂开辟了新的途径。为此，我的生物无机化学研究项目的一个长期目标是开发新一代的生物催化剂，可以与“最先进的”工业方法竞争。此外，随着我们设计、合成和研究新的基于蛋白质的催化剂，我们还将开发一套全面的指标，可用于评估和改善氧化还原功能。我们将讨论电子如何在人造蛋白质中运动的基本问题，以及我们如何最好地利用生物氧化还原机制进行基本的化学转化。

Accelerating climate change demands the development of new technologies that enable access to renewable chemical fuels and feedstocks. Despite the many approaches currently being pursued, catalysis using proteins remains an unrealized resource, especially for redox transformations (e.g., carbon dioxide to methanol). Redox enzymes are ideal candidates for catalysis because they naturally exert exquisite control over the energetic electrons required for complex transformations. Recent advances in our understanding of multistep electron transfer reactions, as well as protein design, open new avenues for investigations of artificially modified protein catalysts. To that end, a long-term goal of my bioinorganic chemistry research program is to develop a new generation of biocatalysts that can compete with “state-of-the-art” industrial approaches. Further, as we design, synthesize, and investigate new protein-based catalysts we will also develop a comprehensive set of metrics that can be used to assess and improve redox functions. We will address fundamental questions about how electrons move in artificial proteins and how we can best exploit biological redox machinery for essential chemical transformations. The proposed research will focus on the following three short-term objectives over the next 5 years: (1) to demonstrate photoelectrochemical catalysis by novel protein + indium tin oxide electrodes; (2) to selectively oxidize organic biopolymers with engineered heme proteins; and (3) to modify metalloproteins for renewable energy redox catalysis. These three complementary research objectives address key hurdles to using enzymes on large scales: constructing devices, optimizing protein catalysis, and elucidating design criteria for new, targeted catalysts. In Objective 1 we will establish methods for immobilizing functional proteins on electrode surfaces (device development). This opens the way for electrochemical- and photo-catalysis. In Objective 2 we focus on careful modifications to the easily obtained protein cytochrome c peroxidase to elicit new redox functions (catalyst optimization). A conservative and systematic approach will provide specific information about structure-function relationships. Ideally, these new systems will be amenable to immobilization strategies developed through Objective 1. Finally, our work on Objective 3 will take a more ambitious tact (designing new catalysts). Starting from very stable, heat tolerant metalloproteins, we will generate proteins with exposed (coordinatively unsaturated) metal sites. Hydrogen bonding and steric constraints make proteins exceptional “ligands” for supporting unusual coordination geometries and imparting unique reactivity upon first-row transition metals. However, few studies have taken advantage of this control to build proteins with reactivity that mirrors or improves upon that of small molecule catalysts. We will produce and extensively characterize artificial proteins to establish design elements, and then investigate the reactivity of the metal sites toward substrates (e.g., reduction of protons to dihydrogen). Taken together, the knowledge gained from this research program will provide new ways to approach our growing need for renewable chemical catalysis as we accelerate a global transition away from fossil fuels. Our work ranges from the development of photoelectrochemical devices (Objective 1) to design and optimization of protein redox catalysts (Objectives 2 and 3). The range of projects in my program will enable new approaches and technologies for catalysis using artificial proteins, while providing fruitful opportunities for the intellectual and professional development of highly qualified personnel in biological inorganic chemistry and catalysis.