Comparison and Analysis of β-ketoacyl-ACP Synthase from Polyketide with Computer and Its Implication on Combinatorial Biosynthesis

Abstract:

For rational design of novel polyketides and improving the combinatorial biosynthesis of polyketides. 26 β-ketoacyl-ACP synthases from several polyketide synthases were analysed with ClustalW、MEGA4.0. The primary parameters, secondary, tertiary structures and active sites of nine of them with different substrate specificity were compared or predicted in detail using ProtParam, Phdsec, Swiss-Model. The results revealed that they have more similarity in structure than in sequence and all own a high percentage of serine in their active sites; in addition, the β-ketoacyl-ACP synthases whose substrates possess two carboxyl groups were found to have a theoretical pI less than 5.0, and their formal charges sum were on the low side too; the conserved sequence of the 26 β-ketoacyl-ACP synthases is V303ELHGTGTPLGDPIEAGA320, but it is away from the active site. These conclusions have promising potential for module or domain substitution and site-specific mutation of polyketide synthases; also providing a reference for the study of their evolution mechanism.