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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.

SUBMITTER: Koehnke J

PROVIDER: S-EPMC4268494 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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The structural biology of patellamide biosynthesis.

Koehnke Jesko J Bent Andrew F AF Houssen Wael E WE Mann Greg G Jaspars Marcel M Naismith James H JH

Current opinion in structural biology 20141125

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 macrocycliza ...[more]

PMID: 25460274

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