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

Publication ,  Journal Article
Malcolmson, SJ; Young, TS; Ruby, JG; Skewes-Cox, P; Walsh, CT
Published in: Proceedings of the National Academy of Sciences of the United States of America
May 2013

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.

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Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

May 2013

Volume

110

Issue

21

Start / End Page

8483 / 8488

Related Subject Headings

  • Thiazoles
  • Streptomyces lividans
  • Protein Structure, Secondary
  • Protein Processing, Post-Translational
  • Protein Precursors
  • Peptides, Cyclic
  • Peptides
  • Molecular Sequence Data
  • Macrocyclic Compounds
  • Bacterial Proteins
 

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Malcolmson, S. J., Young, T. S., Ruby, J. G., Skewes-Cox, P., & Walsh, C. T. (2013). The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds. Proceedings of the National Academy of Sciences of the United States of America, 110(21), 8483–8488. https://doi.org/10.1073/pnas.1307111110
Malcolmson, Steven J., Travis S. Young, J Graham Ruby, Peter Skewes-Cox, and Christopher T. Walsh. “The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds.Proceedings of the National Academy of Sciences of the United States of America 110, no. 21 (May 2013): 8483–88. https://doi.org/10.1073/pnas.1307111110.
Malcolmson SJ, Young TS, Ruby JG, Skewes-Cox P, Walsh CT. The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds. Proceedings of the National Academy of Sciences of the United States of America. 2013 May;110(21):8483–8.
Malcolmson, Steven J., et al. “The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds.Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 21, May 2013, pp. 8483–88. Epmc, doi:10.1073/pnas.1307111110.
Malcolmson SJ, Young TS, Ruby JG, Skewes-Cox P, Walsh CT. The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds. Proceedings of the National Academy of Sciences of the United States of America. 2013 May;110(21):8483–8488.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

May 2013

Volume

110

Issue

21

Start / End Page

8483 / 8488

Related Subject Headings

  • Thiazoles
  • Streptomyces lividans
  • Protein Structure, Secondary
  • Protein Processing, Post-Translational
  • Protein Precursors
  • Peptides, Cyclic
  • Peptides
  • Molecular Sequence Data
  • Macrocyclic Compounds
  • Bacterial Proteins