Polyketides are a large family of secondary metabolites with diverse structures and biological activities. Many of them are clinically important compounds such as anti-biotic, anti-fungal, and anti-cancer drugs [1]. The biosynthesis of polyketide is catalyzed by a collection of enzymes called polyketide synthases (PKSs). The carbon chain of polyketide is formed through the stepwise decarboxylative condensation of acyl-thioester units using coordinated group of PKS domains. The genes encoding PKS are usually clustered with their auxiliary and regulatory elements on genome and their products are classified into type I, II, and III depending on the organization of their domains [2].

 Bacterial aromatic polyketides such as tetracyclines and actinorhodin are polycyclic phenolic compounds that are assembled by type II PKSs with at most two domains. A hallmark of these multi-enzyme complexes is the iterative use of a ketosynthase heterodimer (KS and CLF) that catalyze Claisen condensations of theoesters with malonyl-CoA units [3]. During this process, acyl carrier protein (ACP) delivers malonyl building blocks to the ketosynthase heterodimer. Besides these minimal PKSs components, additional tailoring enzymes such as ketoreductases (KRs), aromatases (AROs), and cyclises (CYCs) are required to modify the highly reactive poly-beta-keto intermediates to specific folding pattern. Typical primary products of type II PKS from the concerted type II PKS actions are polyphenols in seven polyketide chemotypes such as the linear tetracyclines, anthracyclines, benzoisochromanequinones, tetracenomycins, aureolic acids, and the angular angucyclines as well as a group of pentagular polyphenols [4]. Additional modification by numerous elaborate tailoring enzymes such as dimerases, P450 monooxygenases, methyltransferases, and glycosyltransferases can take place to further diversify the phenolic polycycles [5].

[1] Staunton J, Weissman KJ: Polyketide biosynthesis: a millennium review. Nat Prod Rep 2000, 18: 380-416.
[2] Shen B: Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms. Curr Opin Chem Biol 2003, 7:285-95
[3] Hertweck C, Luzhetskyy A, Rebets Y, Bechthold A: Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork. Nat Prod Rep 2007, 24:162-90
[4] Fritzsche K, Ishida K, Hertweck C: Orchestration of discoid polyketide cyclization in the resistomycin pathway. J Am Chem Soc 2008, 130:8307-16
[5] Rix U, Fischer C, Remsing LL, Rohr J: Modification of post-PKS tailoring steps through combinatorial biosynthesis. Nat Prod Rep 2002, 19:542-80

Abbreviation: Unc-unclassified, Ang-Angucyclines, Ant-Anthracyclines, Ben-Benzoisochromanequinones, Pen-Pentangular polyphenols, Tet-Tetracenomycins, Aur-Tetracyclines/aureolic acids

PKMiner includes 280 known type II PKSs identified from 42 known type II PKS gene clusters. For each of type II PKS domain, the above table shows the subfamily, biosynthetic function, total number of domains, total number of subfamilies and the average length present in 280 known type II PKSs

Table shows II PKS domains in each type II PKS gene cluster for each aromatic polyketide chemotypes