Bioinformatical Analysis of the Sequences, Structures and Functions of Fungal Polyketide Synthase Product Template Domains

The product template (PT) domains, specifically in fungal non-reducing polyketide synthases (NR-PKSs), mediate the regioselective cyclization of polyketides dominating the final structures. However, up to date, the systematic knowledge about PT domains has been insufficient. In present study, the relationships between sequences, structures and functions of the PT domains were analyzed with 661 NR-PKS sequences. Based on the phylogenetic analysis, the PT domains were classified into prominent eight groups (I-VIII) corresponding with the representative compounds and cyclization regioselectivity (C2-C7, C4-C9, and C6-C11). Most of the cavity lining residue (CLR) sites in all groups were common, while the regional CLR site mutations resulted in the appearance of finger-like regions with different orientation. The cavity volumes and shapes, even the catalytic dyad positions of PT domains in different groups were corresponding with characteristic cyclization regioselectivity and compound sizes. The conservative residues in PT sequences were responsible for the cyclization functions and the evolution of the key residues resulted in the differentiations of cyclization functions. The above findings may help to better understand the cyclization mechanisms of PT domains and even predict the structural types of the aromatic polyketide products.