摘要
The highly reducing iterative polyketide synthases responsible for lovastatin biosynthesis contains a section homologous to condensation(CON)domain observed in nonribosomal peptide synthetases(NRPSs).In the present study,we expressed the isolated lovastatin CON domain and solved the crystal structure to 1.79 A resolution.The overall structure shows similarity to canonical condensation domains of NRPSs,containing the N-terminal and C-terminal subdomains that resemble enzymes of chloramphenicol acetyltransferase family,whereas distinct structural features are observed at the active site.The acceptor entry of the substrate channel is blocked by a flexible loop,thereby preventing the loading of substrate for a new round of chain elongation.The mutation of conserved catalytic motif located at the midpoint of substrate channel agrees with the incapability of CON to catalyzed amide-bond formation.The structure helps to understand the function of CON in lovastatin biosynthesis.
基金
National Natural Science Foundation of China(31570056,31770068)
Fundamental Research Funds for theCentral Universities
