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Unraveling the Biosynthesis of Dimethyl Indolic Acid, A Key Moiety of the Antibacterial Nosiheptide
Author(s) -
Badding Edward,
Grove Tyler,
Booker Squire
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.573.42
Subject(s) - moiety , chemistry , thiazole , enzyme , biosynthesis , stereochemistry , biochemistry , tryptophan , peptide , penicillin binding proteins , amino acid , combinatorial chemistry , penicillin , antibiotics
Nosiheptide (NOS) belongs to a unique class of thiazole‐containing peptide antibiotics that display formidable activity against a number of pathogenic bacteria. Such bacteria include methicillin resistant Staphylococcus aureus , penicillin‐resistant Streptococcus pneumoniae , and vancomycin‐resistant enterococci . One key structural feature of NOS is an indolic acid ring system. The indolic acid moiety is derived from tryptophan via the action of at least four enzymes. In the first step of the proposed pathway, which is catalyzed by NosL, tryptophan is converted into 3‐methyl indolic acid (MIA). The remaining steps and enzymes involved in formation and installation of MIA into the NOS core have not been definitively determined, but are believed to be catalyzed by the sequential action of NosI, NosK, and NosN. The research described herein is focused on elucidating the mechanism by which the indolic acid moiety is formed and installed with the immediate goal of characterizing NosI, NosK, and NosN and the reactions they catalyze. Additionally through bioinformatic analyses, a protein in the nos operon, NosJ, has a sequence similarity to acyl carrier proteins. We believe that this protein carries the product of NosI to either NosK or NosN.