Fig. 35.4. Novel aromatic polyketides produced from engineered variants of the actinorhodin PKS. Some of the products are derived from an actinorhodin/tetracenomycin (tem) or a frenolamycin/actinorhodin (fre) hybrid.
OH O COOH/
aromatic polyketides, some of which are shown in Fig. 35.4. Subsequent reports of combinatorial biosynthesis using type II PKSs, while generally successful, showed that the hybrid enzyme systems did not always perform as expected [35, 36], which has reduced the ability to design combinatorial biosynthesis libraries from type II PKSs with predictable structures. Additionally, the assignments of the roles of different parts of the ''minimal PKS'' in specifying chain length and point of initial cyclization have been shown to be incorrect, at least for some type II PKSs [37-39]. Despite this limitation, or perhaps because of it, several previously unknown aromatic polyketides have been created, sometimes with quite intricate and unexpected structures (Fig. 35.5). Work on combinatorial biosynthesis of aromatic polyketides
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