NEWS OF THE WEEK
HOW NATURE MAKES EARTH AROMA NATURAL PRODUCTS: Biosynthesis of
geosmin, a terpene responsible for the scent of moist soil, is deciphered
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F YOU HAVE EVER dug into a flower bed, walked through a plowed field being readied for planting, or ventured outside after a gentle rain shower, then you have smelled geosmin, a chemical responsible for the characteristic odor of fresh, moist earth. Brown University chemists now have completed a series of studies unraveling precisely how nature goes about making this bicyclic alcohol (Nat. Chem. Biol, DOI: io.i038/nchembio.2007.29). "One nice thing about geosmin is that essentially everyone has smelled it, even if they did not know what it was or where it comes from," says chemistry professor David E. Cane, who along with graduate students Jiaoyang Jiang and Xiaofei He carried out the research. Geosmin, ubiquitous in the environment, is a terpene produced by a number of microorganisms, including soil bacteria and cyanobacteria (blue-green algae). Scientists have known about the compound for more than 100 years, but it wasn't isolated and structurally characterized until 1965. Besides giving rise to the scent of soil, geosmin and its metabolites can cause undesirable musty smells or off-flavors in water and food. People detect geosmin "at the extraordinarily low threshold of 10 ppt, but no one knows why this should be so or even why geosmin is produced," Cane says. Despite the longtime interest, scientists haven't been able to fully decipher how geosmin is made, until now. In 2003, Cane's group and others identified the gene in the soil bacterium Streptomyces coelicolorthat codes for the enzyme that converts farnesyl diphosphate into germacradienol, which is a geosmin precursor. Farnesyl
diphosphate is a common intermediate in the biosynthesis of hundreds of different terpenes, Cane notes. Cane and coworkers suspected that two or more enzymes catalyzing some unknown combination of steps would be required to convert germacradienol to geosmin. But last year, the researchers were surprised to discover that one enzyme alone catalyzes the conversion of farnesyl diphosphate all the way to geosmin byway of germacradienol (J. Am. Chem. Soc. 2006,128,8128). In completing the work, Cane, Jiang, and He now provide the details of the enzymatic process. The team altered specific amino acids in the enzyme and characterized the chemical products of the mutant enzymes. In doing so, the researchers found that the enzyme folds in such a way that two halves harbor independent active sites with distinct catalytic functions. The N-
OPP = diphosphate ( O P 0 2 O P 0 3 d ~ )
E A R T H Y O D O R A N T A a f u n c t i o n a l bacterial enzyme converts farnesyl diphosphate (left) into germacradienol (center) and subsequently into geosmin (right), which is the volatile compound responsible for the characteristic smell of freshly turned soil. 3HUTTERST0CK
terminal half of the enzyme uses farnesyl diphosphate to crank out germacradienol, which subsequently is handed off to the C-terminal half to complete the transformation into geosmin. The researchers believe that microbiologists working in water purification and in the food and beverage industries will be interested in their finding. By understanding precisely how geosmin is made, a method to block its formation could avoid the sometimes musty taste of water, wine, fish, and other foods, Cane says.—STEVE RITTER
PARTNERSHIPS Merck joins forces with Harvard researchers for drug discovery In an agreement being called "an innovative model for industry/academic partnerships," researchers from Harvard Medical School and Merck & Co.'s Boston R&D center are teaming up to accelerate research in oncology and central nervous system disorders. Six HMS labs will receive funding from Merck, and scientists from both organizations will work together in the two therapeutic areas. Individual academic researchers or projects routinely receive funding from
drug companies, but the Merck agreement with Harvard is unique in that it involves multiple labs working in specific therapeutic areas, says Katherine Gordon, director of business development at HMS. According to Gordon, the pact with Merck represents one route academia is taking to translate basic knowledge about the biology and chemistry of a disease into viable drug candidates. Though the agreement focuses on basic research,
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the parties expect it will lead to products. For HMS, the deal is also a way to advance its science in a challenging funding environment. Earlier this month, Harvard handed out the first round of grants through its new Technology Development Accelerator Fund, established to develop promising life sciences ideas to a point where industry will take interest. For Merck, the collaboration bolsters activities at its Boston lab, which opened in2004.-LISAJARVIS
