Peptide Synthases

ENZ enzyme assays, SC structural composition, MM molecular methods, IL isotopic labeling, IF isotopic fractionation, INH inhibition studies, UNK unknown, LOX lipoxogenase, EPSP synthase 5-enolpyruvylshikimate-3-phosphate, SDH shikimate dehydrogenase, PAL phenylalanine ammonium lyase, PKS polyketide synthase, NRPS nonribosomal peptide synthase 1 Gerwick 1999 2 Liu et al. 1994 3 Boonprab et al. 2003 4 Cvejic and Rohmer 1999 5 Disch et al. 1998 6 Chikaraishi et al. 2006 7 Schwender et al. 2001 8 Schwender et al. 1997 9 Mayes et al. 1993 10 Shick et al. 1999 11 Richards et al. 2006 12 Bouarab et al. 2004 13 Pelletreau et al., unpublished data 14 Dittman and Weigand 2006 15 Rein and Barrone 1999 Empty columns imply no direct evidence of these enzymes from these systems... 

The third type of modularity, the multi-catalytic enzymes using substrate channelling, are of particular interest for synthetic applications. Prominent members are the fatty acid synthases, the polyketide synthases and the non-ribosomal peptide synthases l42-44 . in these large proteins, a number of catalytic domains is combined with accessory domains and allows the catalysis of an entire pathway by a single polypeptide chain. Multi-catalytic enzymes frequently use a swinging arm , which is covalently attached to the intermediary product of one reaction step, and is subsequently able to present this molecule to the next catalytic domain for further... 

Fig. 5.2 Organization of polyketide synthases (PKSs). (A) The type I erythromycin PKS (DEBS) which catalyzes the biosynthesis of 6-dEB. The PKS consists of three polypeptides, DEBSl, DEBS2, and DEBS3, each possessing two modules. (B) The type I epothilone PKS consists of six polypeptides EpoA, EpoB [a non-ribosomal peptide synthase (NRPS)], EpoC, EpoD (possessing four modules), EpoE (possessing two modules), and EpoF. (C) The type II actinorhodin PKS con-...

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