related to degree

• Luo, Xiaozhou, Ph.D. in Chemistry, Scripps Research 2010 - 2016

authors

• Luo, Xiaozhou
• Zambaldo, C.
• Liu, T.
• Zhang, Y.
• Xuan, W.
• Wang, C.
• Reed, S. A.
• Yang, P. Y.
• Wang, R. E.
• Javahishvili, T.
• Schultz, Peter
• Young, Travis Scott

publication date

• March 2016

journal

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

abstract

• Thiopeptides are a subclass of ribosomally synthesized and posttranslationally modified peptides (RiPPs) with complex molecular architectures and an array of biological activities, including potent antimicrobial activity. Here we report the generation of thiopeptides containing noncanonical amino acids (ncAAs) by introducing orthogonal amber suppressor aminoacyl-tRNA synthetase/tRNA pairs into a thiocillin producer strain of Bacillus cereus .We demonstrate that thiopeptide variants containing ncAAs with bioorthogonal chemical reactivity can be further postbiosynthetically modified with biophysical probes, including fluorophores and photo-cross-linkers. This work allows the site-specific incorporation of ncAAs into thiopeptides to increase their structural diversity and probe their biological activity; similar approaches can likely be applied to other classes of RiPPs.

subject areas

• Amino Acid Substitution
• Amino Acids
• Bacillus cereus
• Molecular Structure
• Mutagenesis, Site-Directed
• Peptides
• Protein Engineering
• Protein Processing, Post-Translational
• Recombinant Proteins
• Tandem Mass Spectrometry

keywords

• antibiotic
• biosynthesis
• natural products
• noncanonical amino acid
• thiopeptides

PubMed Central ID

• PMC4822594

International Standard Serial Number (ISSN)

• 0027-8424

Digital Object Identifier (DOI)

• 10.1073/pnas.1602733113

PubMed ID

• 26976568

start page

• 3615

end page

• 3620

volume

• 113

issue

• 13