New role for righty molecules

Researchers have identified a role for rare, right-handed versions of amino acids. This so-called D-form of nature's building blocks allows bacterial cell walls to adapt to changes in the environment, says a study in Science this week -- marking one of the few times the D-aminos have been linked to biological function. Scanning electron microscope image of Vibrio cholerae Image: Wikipedia Commons"If you go back in literature dating 20-40 years ago, it was widely believed that we existed in a strictly 'left-handed' protein world," said linkurl:Steven R. Blanke,;http://mcb.illinois.edu/faculty/profile/1197, a microbiologist at the University of Illinois who was not involved in the study. The current work and a few other recent studies, he said, show that "some biological systems could have possibly evolved to utilize the D-forms of some amino acids more than previously thought." Nineteen of the 20 amino acids found in nature come in two forms, mirror images in structural composition, but until recently it seemed life on Earth used only one of them. L-amino acids were viewed as the building blocks of life, leaving researchers perplexed as to the function of their D-amino siblings. Over the past 20 years, though, studies have gradually begun to identify important roles for D-amino acids as, for example, key components of antibiotics, immunosuppressive drugs, and antitumor agents, and as neurotransmitters in the brain. linkurl:Hubert Lam;http://connects.catalyst.harvard.edu/PROFILES/ProfileDetails.aspx?Person=HL87 and colleagues from Harvard Medical School and Brigham and Women's Hospital stumbled upon the discovery while researching whether the shape of Vibrio cholerae, the bacteria responsible for diarrhea-inducing cholera, could influence its virulence, said linkurl:Matthew Waldor,;http://www.hms.harvard.edu/dms/bbs/fac/Waldor.html, a coauthor of the study. Lam's group was working with cells in which proteins controlling cell shape had been mutated. The researchers noticed that the D-forms but not the L-forms of four amino acids stimulated the bacteria to transition from a rod to a spherical shape. So they joined forces with the chemists Jon Clardy and Dong-Chan Oh, to determine what exactly was happening to the cell. As the mutant V. cholerae cells transitioned between exponential growth as rods to a stationary stage as spheres, the researchers found, L-amino acids got converted into D-amino acids by enzymes called racemases, which alter a molecule's structure around the central carbon. To determine where in the cell wall the suddenly plentiful D-amino acids were doing their remodeling job, the researchers compared wild-type cells to cells further mutated to lack racemases (which were therefore equipped with fewer D-amino acids). In these cells, they found, the elastic polymer peptidoglycan, the main component of cell walls, was thicker but weaker -- evidence that D-aminos had the ability to alter the composition, amount, and strength of a critical cell wall component. The group then set out to test their results on another bacterium. "We chose Bacillus subtilis, Gram-positive bacteria, because it is extremely far from V. cholerae evolutionarily," said Waldor. "But it was also because Bacillus is one of the most studied model microorganisms, and therefore there is a wealth of information on it." As with Vibrio, D-amino acids in B. subtilis affected peptidoglycan synthesis and regulated cell wall structure. The righty molecules, the researchers theorized, may be able to slow metabolic activity in any bacteria cell when resources become scarce or environmental conditions stressful. There are still many unanswered questions about the role of D-amino acids in biological functions. Waldor and his colleagues are working to understand the mechanics of how the D-amino acids are affecting peptidoglycan activity and how these previously unappreciated building blocks might be incorporated into new antibiotics. Both Waldor and Blanke are interested in how racemases convert L- into D-amino acids. "We certainly didn't start on the path of studying amino acids," said Waldor, "but we're excited about what we've uncovered." **__Related stories:__***linkurl:Did lefty molecules seed life?;http://www.the-scientist.com/blog/display/55510/ [16th March 2009]*linkurl:Extending the genetic code;http://www.the-scientist.com/article/display/21537/ [15th August 2003]*linkurl:The cyclical nature of potential new antibiotics;http://www.the-scientist.com/article/display/19805/ [30th July 2001]

New role for righty molecules

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