Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential.

Abstract

Biocascade catalysis has emerged as a defining paradigm in contemporary synthesis, enabling the orchestration of multiple enzymatic transformations within a single vessel. By allowing intermediates to flow seamlessly between successive steps without isolation, cascades emulate the elegance of natural biosynthetic networks while delivering significant gains in atom economy and operational simplicity. The intrinsic chemo-, regio-, and stereoselectivity of enzymes facilitates the construction of architecturally complex, enantiomerically enriched molecules under mild, aqueous, and environmentally benign conditions. In this way, biocascade strategies accelerate the generation of molecular diversity while embodying the principles of sustainable chemistry by reducing energy demand, solvent use, and waste generation. Recent advances in protein engineering, directed evolution, computational enzyme design, and synthetic biology have expanded the scope of enzymatic cascades, transforming nature's catalytic repertoire into scalable synthetic technologies. Landmark studies now demonstrate their transformative potential in the assembly of complex polyketides, bioactive alkaloids, pharmaceuticals, and active pharmaceutical ingredients (APIs), as well as diverse heterocyclic scaffolds of medicinal relevance. Collectively, these achievements underscore the growing significance of biocascade catalysis as a cornerstone of modern synthesis, bridging the ingenuity of biological systems with the imperatives of next-generation drug discovery and sustainable chemical manufacturing.