Elucidation of the Biosynthesis of the Indolic Acid Moiety of the Antibiotic Nosiheptide

Open Access
Author:
Badding, Edward Daisuke
Area of Honors:
Chemistry
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Squire Booker, Thesis Supervisor
  • Przemyslaw Maslak, Honors Advisor
Keywords:
  • Natural Products
  • Thiopeptides
  • Crystal Structure
  • Antibiotics
Abstract:
Nosiheptide (NOS) is a highly modified thiopeptide natural product produced by Streptomyces actuosus that belongs to a unique class of thiazole-containing peptide antibiotics. Recent studies have shown that NOS is as an effective antibacterial agent against a number of pathogenic bacteria, such as methicillin resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci. One key structural feature of NOS is an indolic acid ring system, characteristic of e series thiopeptides, which derives from the amino acid tryptophan. In the first step of the proposed pathway, catalyzed by NosL, tryptophan is converted into 3-methyl-2-indolic acid (MIA). The remaining steps and enzymes involved in the formation and installation of MIA into the NOS core have not yet been definitively determined, but are believed to be catalyzed by the sequential action of four enzymes: NosI, NosK, NosL and NosN. The research herein investigates and elucidates the biosynthesis of the indole moiety through analytical and spectroscopic methods.