title: The structural biology of patellamide biosynthesis.
abstract: The biosynthetic pathways for patellamide and related natural products have recently been studied by structural biology. These pathways produce molecules that have a complex framework and exhibit a diverse array of activity due to the variability of the amino acids that are found in them. As these molecules are difficult to synthesize chemically, exploitation of their properties has been modest. The patellamide pathway involves amino acid heterocyclization, peptide cleavage, peptide macrocyclization, heterocycle oxidation and epimerization; closely related products are also prenylated. Enzyme activities have been identified for all these transformations except epimerization, which may be spontaneous. This review highlights the recent structural and mechanistic work on amino acid heterocyclization, peptide cleavage and peptide macrocyclization. This work should help in using the enzymes to produce novel analogs of the natural products enabling an exploitation of their properties.
authors.affiliation: BSRC, North Haugh, The University, St Andrews, KY16 9ST.
authors.forename: Jesko
authors.initials: J
authors.lastname: Koehnke
authors.affiliation: BSRC, North Haugh, The University, St Andrews, KY16 9ST.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Bent
authors.affiliation: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, AB24 3UE.|Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD.
authors.forename: Wael E
authors.initials: WE
authors.lastname: Houssen
authors.affiliation: BSRC, North Haugh, The University, St Andrews, KY16 9ST.
authors.forename: Greg
authors.initials: G
authors.lastname: Mann
authors.affiliation: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, AB24 3UE.
authors.forename: Marcel
authors.initials: M
authors.lastname: Jaspars
authors.affiliation: BSRC, North Haugh, The University, St Andrews, KY16 9ST.
authors.forename: James H
authors.initials: JH
authors.lastname: Naismith
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000096:biosynthesis / Q000737:chemistry; D001419:Bacteria / Q000378:metabolism; D053898:Biosynthetic Pathways; D004122:Dimethylallyltranstransferase / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D000596:Amino Acids; D006571:Heterocyclic Compounds; D010456:Peptides, Cyclic; D004122:Dimethylallyltranstransferase