Increasing cytochrome P450 enzyme diversity by identification of two distinct cyclodipeptide dimerases

• Published in: Chemical communications (Cambridge, England) Vol. 56; no. 75; pp. 1142 - 1145
• Main Authors: Liu, Jing, Xie, Xiulan, Li, Shu-Ming
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 22.09.2020
• Subjects: cytochrome P-450; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Cytochromes P450; Dimerization; Enzymes; heterologous gene expression; Molecular Conformation; operon; Peptides, Cyclic - chemistry; Peptides, Cyclic - genetics; Peptides, Cyclic - metabolism; Saccharopolyspora; Saccharopolyspora - enzymology; stereospecificity
• ISSN: 1359-7345; 1364-548X; 1364-548X
• DOI: 10.1039/d0cc04772d

Genome mining revealed the presence of two cdps-p 450 operons in Saccharopolyspora antimicrobica . Heterologous expression, biochemical characterisation and structure elucidation proved that the two P450 enzymes catalyse distinct regio- and stereospecific dimerizations of cyclo -( l -Trp- l -Trp), which significantly expands the repertoire of diketopiperazine-tailoring enzymes. TtpB1 connects the monomers via C3-C3′, both from the opposite side of H-11/H-11′, while TtpB2 is characterised as the first P450 to mainly catalyse the unusual linkage between N1′ and C3 from the H-11 side. Two P450 enzymes were characterised to catalyse distinct regio- and stereospecific dimerizations of cyclo -( l -Trp- l -Trp), differing from those previously reported in actinobacteria.