Although the macrocyclization of peptides confer protection to proteolytic degradation, improve their membrane solubility and target specificity, the manufacture of macrocycles relies on challenging chemical synthesis. Enzyme-mediated macrocyclization provides promising alternatives to conventional methodologies.

 We recently identified a new type of peptide cyclase, SurE in biosynthesis of non-ribosomal cyclic peptides, surugamides (1). When the surE gene was disrupted by double crossover method, the resultant DsurE strain abolish the production of both type of surugamides. Successive gene complementation restored their productions, showing that SurE is involved in biosynthesis of both types of surugamides. When the recombinant SurE protein was incubated with synthetic peptides mimicking linear precursor of octapeptide and decapeptide, both of them were efficiently converted cyclic products (1,2). The structures of enzymatic products were validated by comparison with synthetic standards. Since SurE accepted structurally unrelated octa- and deca-peptides, we next investigate its substrate scope using array of synthetic substrate derivatives. This revealed that SurE possesses strict specificity against the residue at both ends and relaxed specificity against the residues at the middle of substrate peptides. SurE is potentially applicable as a biocatalyst for peptide cyclization reaction and a genetic tool for synthetic biology.