The structural biology of patellamide biosynthesis

Jesko Koehnke, Andrew F. Bent, Wael E. Houssen, Greg Mann, Marcel Jaspars*, James H. Naismith

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)
6 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)112-121
Number of pages10
JournalCurrent opinion in structural biology
Volume29
DOIs
Publication statusPublished - Dec 2014

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