Multimodular biocatalysts for natural product assembly

Nonribosomal peptides and polyketides represent a large class of natural pr oducts that show an extreme structural diversity and broad pharmacological relevance. They are synthesized from simple building blocks such as amino o r carboxy acids and malonate derivatives on multimodular enzymes called non ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), resp ectively. Although utilizing different substrates, NRPSs and PKSs show stri king similarities in the modular architecture of their catalytic domains an d product assembly-line mechanism. Among these compounds are well known ant ibiotics (penicillin, vancomycin and erythromycin) as well as potent immuno suppressive agents (cyclosporin, rapamycin and FK 506). This review focuses on the modular organization of NRPSs, PKSs and mixed NRPS/PKS systems and how modules and domains that build up the biosynthetic templates can be exp loited for the rational design of recombinant enzymes capable of synthesizi ng novel compounds.