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.