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Firefly luciferase, a luminescence-inducing enzyme, is often engineered into cells to facilitate imaging in studies on the mechanisms of cancer and other diseases. However, it differs by only a single amino acid from fatty acyl-CoA synthetase, an enzyme that plays a key role in fatty acid metabolism. This close resemblance has raised concerns that luciferase-engineered cells could have adverse effects on metabolism and thus cause experimental artifacts that might invalidate some of the many studies—estimated to number about 30,000—in which luciferase has been used. Peter J. O’Brien of the drug company Pfizer, Gary Siuzdak of Scripps Research Institute California, and coworkers have now put that fear to rest (Metabolomics 2014, DOI: 10.1007/s11306-014-0622-5). The researchers used mass spectrometry studies to show that there are no significant metabolic differences between native and luciferase-engineered cells in three cell lines commonly used in cancer research. “Fortunately for the thousands of investigators who use this technology, our results came back negative with no statistically significant variance observed in the cancer cells we examined,” Siuzdak says. “This negative result is ultimately very positive.”
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