Cyclasen

Cyclasen is a proposed family of cyclase enzymes involved in the biosynthesis of cyclic compounds in microorganisms. The term describes enzymes that catalyze intramolecular cyclization to convert linear precursors into cyclic products, increasing structural diversity in natural product pathways such as polyketides and nonribosomal peptides. The concept arose from comparative genomics identifying conserved motifs linked to ring formation in several biosynthetic clusters.

Mechanism and structure: Most characterized cyclasen-like enzymes are oxidoreductases or lyases that act on alkenyl or amino substrates and often require cofactors such as NAD(P)H or metal ions. They can proceed via radical, dehydration, or condensation mechanisms. Structurally, they show a core fold related to other cyclases, typically with a Rossmann-like domain and a substrate-oriented active-site loop.

Distribution and significance: Reported in actinomycetes and cyanobacteria, cyclasen enzymes are linked to diverse cyclic frameworks, including macrocyclic lactones and cyclic peptides. Their activity affects product yield and stereochemistry, making them targets for metabolic engineering.

Applications and engineering: In labs, engineered cyclasen variants enable access to novel cyclic scaffolds by altering catalytic residues or domain architectures, supporting the development of macrocyclic drugs and other cyclic molecules.

Safety and regulation: As with enzyme-catalyzed processes, cyclasen-based production requires containment, and assessment of byproducts and potential allergenicity before industrial use.