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Science 325 (5947): 1552-1555

Copyright © 2009 by the American Association for the Advancement of Science

D-Amino Acids Govern Stationary Phase Cell Wall Remodeling in Bacteria

Hubert Lam,1,* Dong-Chan Oh,2,*,{dagger} Felipe Cava,1,* Constantin N. Takacs,1,{ddagger} Jon Clardy,2 Miguel A. de Pedro,3 Matthew K. Waldor1,§

Abstract: In all known organisms, amino acids are predominantly thought to be synthesized and used as their L-enantiomers. Here, we found that bacteria produce diverse D-amino acids as well, which accumulate at millimolar concentrations in supernatants of stationary phase cultures. In Vibrio cholerae, a dedicated racemase produced D-Met and D-Leu, whereas Bacillus subtilis generated D-Tyr and D-Phe. These unusual D-amino acids appear to modulate synthesis of peptidoglycan, a strong and elastic polymer that serves as the stress-bearing component of the bacterial cell wall. D-Amino acids influenced peptidoglycan composition, amount, and strength, both by means of their incorporation into the polymer and by regulating enzymes that synthesize and modify it. Thus, synthesis of D-amino acids may be a common strategy for bacteria to adapt to changing environmental conditions.

1 Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA 02115, USA.
2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
3 Centro de Biología Molecular "Severo Ochoa" Consejo Superior de Investigaciones, Científicas-Universidad Autónoma de Madrid, Facultad de Ciencias, 28049 Madrid, Spain.

* These authors contributed equally to this work.

{dagger} Present address: Natural Products Research Institute, College of Pharmacy, Seoul National University, San 56-1, Sillim, Seoul 151-742, Republic of Korea.

{ddagger} Present address: Yale University, New Haven, CT 06520, USA.

§ To whom correspondence should be addressed. E-mail: mwaldor{at}

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