Ten years of efforts, nature released breakthrough protein new technology

Chemists from the University of California, San Diego, have developed a new method that for the first time gives scientists the ability to attach chemical markers to proteins in a repeatable cycle and then remove them Their research, published online this week in the journal Nature methods, will give researchers a better understanding of the biochemistry of naturally occurring proteins to create better antibiotics, anticancer drugs, biofuels and other natural products In addition, it provides scientists with a new test tool that can be used to purify and track proteins in living cells This is the result of 10 years' efforts by researchers in Michael Burkart's laboratory, a professor of chemistry and biochemistry at the University of California, San Diego They have developed a new method to attach chemical markers to specific sites on proteins and selectively remove them This flexibility allows researchers to use a variety of different functional accessories to study proteins, providing versatility similar to the biochemical Swiss Army knife The advantage of this technology lies in the wide flexibility of its accessories Each of these accessories can be used for different purposes and biological research The goal of Burkart's laboratory is to learn more about the biochemical signaling pathway of fatty acid metabolism and the biosynthesis of other natural products One of the projects focuses on the transformation of algae to produce improved biofuels In this regard, scientists hope to maximize the production of high-quality seaweed oil, which can be used to supplement or replace existing chemical fuels "In fatty acid metabolism, fatty acids grow out of one arm, end up twining and begin to interact with metabolic proteins," Burkart said We want to know how long the growing fatty acids are before they start binding to proteins? " Burkart and his lab chemists have found a way to remove the chemical signature of this metabolic protein using phosphodiesterase from the common bacterium Pseudomonas aeruginosa A fatty acid analogue is then attached to reconstruct the protein complex to its natural state By repeating this process over and over again, and using nuclear magnetic resonance (NMR) to detect the molecular changes in fatty acids at different stages of metabolism, scientists have recorded the biochemical signal pathways of fatty acid metabolism in a way that was previously impossible "Without this tool, we really have only limited methods to study the dynamics of these basic metabolic processes," Burkart said It opens the door for us to study the fatty acid biosynthesis shared by algae in detail If you want to design methods to improve the oil production of algae, or to generate different kinds of oil molecules in algae that are more suitable for biofuels, this is what you have to understand " Chemists at the University of California, San Diego, also used NMR to confirm that chemical removal and addition of chemical probes did not degrade or alter proteins in any way "We have shown that we can do this repeatedly, at least four or five times, without any protein degradation The protein is still very stable and easy to study, "Burkart said Because these same metabolic processes are shared by the metabolism of many natural products, including anticancer drugs, antibiotics and natural pesticides, Burkart said the new tool should be widely used in natural product chemistry laboratories "We still don't fully understand these basic biochemical pathways," he said We are now in the process of understanding the mechanism of these basic biosynthetic enzymes Most drugs come from natural products, and many drugs in the future can come from these signaling pathways Now scientists have great interest in synthetic biology, using these signal pathways to generate new antibiotics or new anticancer drugs They are all regulated by these same types of interactions " Chemists at the University of California, San Diego, say their method of labeling and removing chemical probes should be used as a common laboratory tool for imaging and tracking proteins in living cells, as well as for manipulating extracellular proteins "An adherent label, such as biotin, enables the protein to be purified," Burkart said Another can cut off the label and attach a fluorescent molecule to monitor the interaction of proteins with other molecular chaperones This method can also be used to study living cells, for example, to observe the protein expression level of the whole cell life cycle We can see it as a possible application " "Dr Burkart's new labeling technology provides scientists with an unprecedented way to explore the complex catalytic mechanisms associated with the biosynthesis of natural products," said Barbara gerratana, of the National Institute of Integrated Medical Sciences, part of the funding for the study The technology will help scientists use these natural biochemical signaling pathways to synthesize new molecules for a wide range of applications, including basic biomedical research and drug discovery "