The direct functionalization of C–H bonds constitutes a powerful strategy to construct and diversify organic molecules. However, controlling the chemo- and site-selectivity of this transformation, particularly in complex molecular settings, represents a significant challenge. Metalloenzymes are ideal platforms for achieving catalyst-controlled selective C–H bond functionalization as their reactivities can be tuned by protein engineering and/or redesign of their cofactor environment. In this review, we highlight recent progress in the development of engineered and artificial metalloenzymes for C–H functionalization, with a focus on biocatalytic strategies for selective C–H oxyfunctionalization and halogenation as well as C–H amination and C–H carbene insertion via abiological nitrene and carbene transfer chemistries. Engineered heme and nonheme iron dependent enzymes have emerged as promising scaffolds for executing these transformations with high chemo-, regio-, and stereocontrol as well as tunable selectivity. These emerging systems and methodologies have expanded the toolbox of sustainable strategies for organic synthesis and created new opportunities for the generation of chiral building blocks, the late-stage C–H functionalization of complex molecules, and the total synthesis of natural products.

C-H键的直接功能化构成了构建和多样化有机分子的有力策略。然而，控制这种转化的化学选择性和位点选择性，特别是在复杂的分子环境中，是一项重大挑战。金属酶是实现催化剂控制的选择性 C-H 键功能化的理想平台，因为它们的反应性可以通过蛋白质工程和/或辅因子环境的重新设计来调节。在这篇综述中，我们重点介绍了用于 C-H 官能化的工程化和人工金属酶开发的最新进展，重点是选择性 C-H 氧官能化和卤化以及 C-H 胺化和 C-H 卡宾插入的生物催化策略非生物氮烯和卡宾转移化学。工程化的血红素和非血红素铁依赖性酶已成为具有高化学、区域和立体控制以及可调选择性的执行这些转化的有前途的支架。这些新兴的系统和方法扩展了有机合成可持续战略的工具箱，并为手性构件的生成、复杂分子的后期 C-H 官能化以及天然产物的全合成创造了新的机会。