Intramolecular cyclizations of polyketide biosynthesis: mining for a "Diels-Alderase"?
Despite the large number of naturally occurring metabolites existing for which enzymatic Diels-Alder reactions have been proposed as a key biosynthetic step, the actual number of enzymes thus far identified for these transformations is incredibly low. Even for those few enzymes identified, there is currently little biochemical or mechanistic evidence to support the label of a "Diels-Alderase." For several families of polyketide metabolites, the transformation in question introduces a rigid, cross-linked scaffold, leaving the remaining peripheral modifications and polyketide processing to provide the variation among the related metabolites. A detailed understanding of these modifications--how they are introduced and the tolerance of enzymes involved for alternate substrates--will strengthen biosynthetic engineering efforts toward related designer metabolites. This review addresses intramolecular cyclizations that appear to be consistent with enzymatic Diels-Alder transformations for which either the responsible enzyme has been identified or the respective biosynthetic gene cluster for the metabolite in question has been elucidated.
Kelly
Wendy L
WL
School of Chemistry and Biochemistry and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA. wendy.kelly@chemistry.gatech.edu
D001419:Bacteria / Q000201:enzymology* / Q000378:metabolism; D003500:Cyclization; D005658:Fungi / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D018942:Macrolides / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism
D018942:Macrolides; D009097:Multienzyme Complexes; C408144:macrophomate synthase; D048630:Polyketide Synthases