Natural sources, including microbes, fungi, and plants are a rich reservoir of complex molecules with diverse and potent biological activities, yet the structural complexity of these compounds often makes them challenging to access using traditional synthetic chemistry. Nature addresses this challenge through tailored biosynthetic pathways that rely on sophisticated enzyme catalysts. Of particular interest are enzymes capable of achieving carbon–carbon (C–C) bond formation, a cornerstone of organic synthesis required to construct the framework of organic molecules. Inspired by nature’s strategies, this work leverages enzymes from natural product pathways as powerful tools for C–C bond formation. By integrating traditional synthetic methods with enzyme-catalysed transformations, we explore biocatalysts that exhibit broad substrate scope, high catalytic efficiency, and exceptional site- and stereoselectivity. Together, these approaches allow access to diverse molecular scaffolds, while adding biosynthetic enzymes to the toolkit of synthetic chemists in the quest for the most efficient and environmentally conscious methods to construct complex organic molecules.