Work

Marine Molecular Machines: Heterocyclization in Cyanobactin Biosynthesis

Year: 2010

Type: article

Abstract: Natural products that contain amino-acid-derived (Cys, Ser, Thr) heterocycles are ubiquitous in nature, yet key aspects of their biosynthesis remain undefined. Cyanobactins are heterocyclic ribosomal peptide natural products from cyanobacteria, including symbiotic bacteria living with marine ascidians. In contrast to other ribosomal peptide heterocyclases that have been studied, the cyanobactin heterocyclase is a single protein that does not require an oxidase enzyme. Using this simplifying condition, we provide new evidence to support the hypothesis that these enzymes are molecular machines that use ATP in a product binding or orientation cycle. Further, we show that both protease inhibitors and ATP analogues inhibit heterocyclization and define the order of biochemical steps in the cyanobactin biosynthetic pathway. The cyanobactin pathway enzymes, PatD and TruD, are thiazoline and oxazoline synthetases.

Source: ChemBioChem

DOI: 10.1002/cbic.201000196

Authors: John A. McIntosh, Eric W. Schmidt

Institution: University of Utah

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: Sanofi, National Institutes of Health, National Institute of General Medical Sciences

Awards: Symbiont Models for Natural Product Pathway Manipulation, G635527312