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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Straight, Paul D. Schroeder, Frank C. Clardy, Jon Fischbach, Michael A. Butcher, Rebecca A. Kolter, Roberto Walsh, Christopher T. |
| Description | Author Affiliation: Butcher RA ( Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.); |
| Abstract | The approximately 80-kb pksX gene cluster in Bacillus subtilis encodes an unusual hybrid polyketide/nonribosomal peptide synthase that has been linked to the production of the uncharacterized antibiotic bacillaene. Multiple copies of this synthase, each similar in size to the ribosome, assemble into a single organelle-like complex with a mass of tens to hundreds of megadaltons. The resource requirements of the assembled megacomplex suggest that bacillaene has an important biological role. By coupling a differential NMR spectroscopic technique with genetically manipulated strains of B. subtilis, we were able to characterize the structure of this unusual secondary metabolite, which could not be predicted by using bioinformatic analysis. We report that bacillaene is a linear molecule with two amide bonds: the first links an alpha-hydroxy carboxylic acid to a omega-amino carboxylic acid containing a conjugated hexaene, and the second links the hexaene-containing carboxylic acid to an (omega-1) amino carboxylic acid containing a conjugated triene. Knowledge of bacillaene's structure has enabled us to annotate the pksX gene cluster and should facilitate the study of bacillaene's biosynthesis as well as its biological role in B. subtilis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Bacillus Subtilis Metabolism Computational Biology Multigene Family Peptide Synthases Chemistry Polyenes Biological Assay Carboxylic Acids Magnetic Resonance Spectroscopy Mass Spectrometry Models, Chemical Peptides Spectrophotometry Stereoisomerism Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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