Lemon Christopher M
Department of Chemistry and Biochemistry, Montana State University, PO Box 173400, Bozeman, MT 59717, United States.
J Inorg Biochem. 2023 Sep;246:112282. doi: 10.1016/j.jinorgbio.2023.112282. Epub 2023 Jun 5.
Heme proteins perform diverse biochemical functions using a single iron porphyrin cofactor. This versatility makes them attractive platforms for the development of new functional proteins. While directed evolution and metal substitution have expanded the properties, reactivity, and applications of heme proteins, the incorporation of porphyrin analogs remains an underexplored approach. This review discusses the replacement of heme with non-porphyrin cofactors, such as porphycene, corrole, tetradehydrocorrin, phthalocyanine, and salophen, and the attendant properties of these conjugates. While structurally similar, each ligand exhibits distinct optical and redox properties, as well as unique chemical reactivity. These hybrids serve as model systems to elucidate the effects of the protein environment on the electronic structure, redox potentials, optical properties, or other features of the porphyrin analog. Protein encapsulation can confer distinct chemical reactivity or selectivity of artificial metalloenzymes that cannot be achieved with the small molecule catalyst alone. Additionally, these conjugates can interfere with heme acquisition and uptake in pathogenic bacteria, providing an inroad to innovative antibiotic strategies. Together, these examples illustrate the diverse functionality that can be achieved by cofactor substitution. The further expansion of this approach will access unexplored chemical space, enabling the development of superior catalysts and the creation of heme proteins with emergent properties.
血红素蛋白利用单一的铁卟啉辅因子执行多种生化功能。这种多功能性使其成为开发新型功能蛋白的有吸引力的平台。虽然定向进化和金属取代扩展了血红素蛋白的性质、反应性和应用，但卟啉类似物的掺入仍然是一种未被充分探索的方法。本综述讨论了用非卟啉辅因子（如卟吩、咕啉、四脱氢卟啉、酞菁和双水杨醛缩邻苯二胺）取代血红素，以及这些缀合物的相关性质。虽然结构相似，但每个配体都表现出独特的光学和氧化还原性质，以及独特的化学反应性。这些杂化物作为模型系统，用于阐明蛋白质环境对卟啉类似物的电子结构、氧化还原电位、光学性质或其他特征的影响。蛋白质封装可以赋予人工金属酶独特的化学反应性或选择性，这是单独使用小分子催化剂无法实现的。此外，这些缀合物可以干扰致病细菌中血红素的获取和摄取，为创新的抗生素策略提供了一条途径。总之，这些例子说明了通过辅因子取代可以实现的多种功能。这种方法的进一步扩展将进入未被探索的化学空间，从而能够开发出更优异的催化剂，并创造出具有新特性的血红素蛋白。
