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Researchers show fruit flies have latent bioluminescence
Date:4/10/2014

bioluminescent reaction similar to the firefly. The key was finding a small molecule to fill the role of D-luciferin, which is not a substrate for ACSLs, to kick start the biochemical reaction.

Suspecting that D-luciferin was in fact a poor substrate for ACSLs due to its shape, Miller and colleagues David Mofford, a fourth year doctoral candidate in the Graduate School of Biomedical Sciences and first author of the study and Randheer Gadarla, PhD, postdoctoral research fellow, tested a number of synthetic luciferins he had developed to see if they had the geometry necessary to initiate bioluminescence using the fatty acyl-CoA synthetase CG6178 found in the fruit fly Drosophila melanogaster.

Miller found that when this fruit fly protein was treated with a rigid synthetic analog of D-luciferin, named CycLuc2, it emitted a red glow. Simply adding CycLuc2 to live Drosophila cells was sufficient to make them glow as well. When CG6178 was expressed in mammalian cells, they too were able to emit light in the presence of CycLuc2.

"We think the unique rigid and asymmetric ring structure of the synthetic CycLuc2 molecule acts as a handle to help properly align it within the enzyme so adenylation can occur. Once that happens, the molecule can be oxidized to emit light," said Miller. "D-luciferin doesn't fit properly so the biochemical reaction necessary to initiate bioluminescence can't get started."

These findings suggest that other bioluminescent enzymatic activities may already exist in nature, waiting to be revealed by a suitable luciferin analog. Having multiple luciferases with unique substrates increases the amount of information that can be gained using this technique. And because it doesn't require changing the underlying DNA, utilizing endogenous proteins as luciferases could greatly impact the potential uses of bioluminescence imaging to study gene expression, understand infection, track cancer cells, or gauge
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Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School
Source:Eurekalert

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