Polyketide cyclase

B Shen, RG Summers, E Wendt-Pienkowski, CR Hutchinson. The Streptomyces glaucescens TcmKL polyketide synthase and TcmN polyketide cyclase genes govern the size and shape of aromatic polyketides. J Am Chem Soc 117 6811-6821, 1995. 

Figure 6 (A) Reactions catalyzed by aromatic cyclases and aromatases. These enzymes control the diverse cyclization patterns of aromatic polyketides and in general display high regioselectivity and substrate specificity. (B) Examples of known products with different cyclization patterns that are accessible via the thioesterase (TE) domain of DEBS.

Fig. 4. Polyketide biosynthesis by gene products of the act PKS cluster. Presence of the KS/AT, CLF, and ACP is sufficient for the production of two 16-carbon polyketides, SEK4 and SEK4b both in vivo [ 103] and in vitro [107]. In the presence of the act ketoreductase (KR), aromatase (ARO) and cyclase (CYC), the octaketide intermediate is converted into DMAC. DMAC can be converted into 8-methoxy DMAC both in vivo and in vitro through the S-adenosylmethionine (Adomet)-dependent action of the tcmO methyltransferase [207]...

Fuji I, Watanabe A, Sankawa U, Ebizuka Y. Identification of a claisen cyclase domain in fungal polyketide synthase WA, a naphthpyrone synthase of Aspergillus nidulans. Chem. Biol. 2001 8 189-197. 

Figure 4. Organization of representative type 1, II, and III polyketide synthases. Upper modular arrangement of DEBS 1,2,3 subunits Center orientation and arrangement of open reading frames in actinorhodin gene cluster Lower chalcone synthase subunit. AT, acyltransferase ACP, acyl carrier protein KS, ketosynthase KR, ketoreductase DH, dehydratase ER, enoyl reductase TE, thioesterase TA, tailoring enzyme R/T, regulatory/transport related AR aromatase CY, cyclase.

Type II PKS complexes are comprised at a minimum of four types of subunits encoded by discrete open reading frames acyl carrier protein, ketosynthase a, ketosynthase p (also referred to as chain length factor ), and a malonyl CoA acyltransferase responsible for loading acyl-CoA extender units on to the acyl carrier protein subunit (34 Fig. 4). Additional subunits containing ketoreductase, cyclase, or aromatase activity may also occur in more complex type II synthases. Typically, the four core subunits (acyl carrier protein, ketosynthase a, ketosynthase p, and malonyl-CoA acyltransferase) participate in the iterative series of condensation reactions until a specified polyketide chain length is achieved, then folding and cyclization reactions yielding the final... 

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