The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds.

Journal Article

Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin cluster from Streptomyces bernensis UC 5144, its heterologous expression in Streptomyces lividans TK24 and Streptomyces venezuelae ATCC 10712, and detection of variant and incompletely processed scaffolds. Posttranslational maturation in S. lividans of both the wild-type berninamycin prepeptide (BerA) and also a T3A mutant generates macrocyclic compounds as well as linear variants, which have failed to form the pyridine and the macrocycle. Expression of the gene cluster in S. venezuelae generates a variant of the 35-atom skeleton of berninamycin, containing a methyloxazoline in the place of a methyloxazole within the macrocyclic framework.

Full Text

Duke Authors

Cited Authors

  • Malcolmson, SJ; Young, TS; Ruby, JG; Skewes-Cox, P; Walsh, CT

Published Date

  • May 21, 2013

Published In

Volume / Issue

  • 110 / 21

Start / End Page

  • 8483 - 8488

PubMed ID

  • 23650400

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1307111110

Language

  • eng

Conference Location

  • United States