Polyketide Synthase Classification

As previously mentioned, PKSs can be grouped into different classes on the basis of their molecular architecture and to some extent their mode of action. The major divisions are into types I, II and III (Fig. 1.6) [17, 18]. Type 1 PKSs, which can be further subdivided, are primarily found in bacteria and fnngi, whereas lype II PKSs are exclusive to bacteria. Type III PKSs are predominantly observed in plants, however some examples are known in bacteria and fnngi. 

As highlighted in Fig. 1.6, the class of type I PKSs can be fnrther snb-divided based purely on enzymatic architecture. The iterative type I PKSs are found in both bacteria and fungi, whereas the modular type I PKSs are exclusive to bacteria. 

Relatively recently a class of modular type 1 PKSs have been discovered which do not conform to the textbook colinearity rules [15]. In these particular systems, the domain organisation rarely correlates with the polyketide product due to the high diversity of non-canonical modules that often contain novel enzymatic domains. The most noticeable feature of these clusters, however, is the absence of integral AT domains within the PKS. Instead, the AT activity is supplied by a reduced number of free-standing enzymatic domains servicing every module in the entire cluster (Fig. 1.9) [25]. These systems are therefore termed trans-AT PKSs, of which the pederin PKS is an example (Fig. 1.10) [26]. In contrast, the 6-dEB system is an example of a c -AT PKS, where the AT domains are integral to the PKS, with an AT domain within each module (Fig. 1.8). 

Phylogenetic studies have shown that the cis- and trans-AI PKSs have evolved independently from FASs and, although both systems appear very similar, the tvans-AT PKSs harbour far more enzymatic functionality than their cis-AT counterparts [27, 28]. As a result, many more module variations exist for trans-AI systems. Eight modnle variants are known for cis-AT PKSs KS-AT-ACP, KS-AT-KR-ACP, KS-AT-DH-KR-ACP, KS-AT-DH-KR-ER-ACP and their MT-based ana-lognes. In contrast, over 50 module architectures have already been identified in trans-AT PKSs [15]. 

A feature that is archetypal of trans-KH PKSs is the presence of non-elongating KS domains (KS ), which usually lack a crucial catalytic histidine residue required for elongation. These KS domains are often located within modules split over two proteins, and within the domain sequence KS-KR-ACP-KS //DH-ACP that generates Z-configured double bonds [15, 27], 

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Liu, W., Ahlert, J., Gao, Q. et al. (2003) Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model. Proceedings of the National Academy of Sciences of the United States of America, 100, 11959. 

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