heemsynthesis

Heemsynthesis is a term used to describe a set of techniques and concepts in chemistry and biotechnology aimed at constructing and integrating heme-containing cofactors into enzymes and catalytic systems to enable new reactivities. The field encompasses both chemical synthesis of heme or heme-like porphyrins and their incorporation into protein or protein-free scaffolds to create functional holoenzymes and artificial catalysts. By combining synthetic cofactors with biological or semi-synthetic frameworks, heemsynthesis seeks to expand the range of transformations available to biocatalysts and chemocatalysts alike.

The term emerged in late 2010s discussions of biohybrid catalysis and cell-free systems, where researchers sought ways to overcome limitations of native enzymes, such as substrate scope or operational stability, through the introduction of chemically tailored heme units. Key ideas include modular assembly, tuning of the porphyrin environment, and compatibility with non-native substrates and reaction conditions.

Core approaches in heemsynthesis include the chemical synthesis of diverse heme analogs, reconstitution of these cofactors into apoproteins or into synthetic scaffolds, and the development of hybrid systems that pair natural protein frameworks with non-natural heme groups. Methods span traditional cofactor reconstitution, semi-synthetic chemistry, and cell-free or immobilized platforms to enhance stability and recyclability.

Applications span industrial biocatalysis, sustainable oxidation and hydroxylation processes, electrocatalysis, and biosensing. While promising, challenges remain, including cost, scalability, cofactor stability, and compatibility with complex substrates. Ongoing work aims to broaden substrate scope, improve turnover, and integrate heemsynthesis-derived catalysts into practical workflows. See also: heme, porphyrins, biocatalysis, enzyme engineering.