Life-saving chemical compounds are traditionally created using hundreds of thousands of dollars and multiple years in the lab, but Dr. David Michaelis, a professor in the Department of Chemistry and Biochemistry, is currently working on a process that could revolutionize the pharmaceutical industry.
The process is called “assembly line biosynthesis,” and compounds that today may take several years and millions of dollars to create might someday be widely available for consumer use.
Michaelis and his team have focused on the problem of creating cancer-toxic compounds and have started developing the assembly line approach with nature as an inspiration.
“Nature has an amazing ability to generate really complex molecules, which in many instances also have important drug properties,” Michaelis said. “One way nature is able to assemble these challenging molecules—often in a single cell—is by using an assembly line of enzymes that puts the molecule together piece by piece. The Michaelis lab is seeking to mimic this natural process using chemical tools rather than enzymes, in a process they have coined ‘assembly-line chemical synthesis.’”
A lot of cancer research is focused on adapting nature’s compounds to human bodies. Michaelis wants to take it one step further. Instead of using the compounds as a model, he wants to use nature’s processes.
“We want to be able to design any molecule we can envision as a drug candidate and synthesize it with the same efficiency that nature achieves,” Michaelis said. “This has the potential to dramatically reduce the cost of new drugs, making life-saving drugs more available to the world.”
Michaelis and his team are working together to create a structure, the “assembly line,” that mimics the helix structures found in nature.
“Nature often uses helical poly-amino acid structures to build enzyme active sites,” Michaelis said. “We want to use this same type of structure to design our catalysts and build our assembly lines.”
Each section of the helix will provide a different surface on which catalysts may be placed. When the chemical compounds are fed through this assembly line, made up of different surface catalysts, the compound will have gone through many different chemical processes in a very short amount of time.
“This ‘assembly line’ method is very different from the way scientists create complex compounds now,” Michaelis said. “Chemists traditionally use a reaction by reaction approach to drug compounds, which is time intensive and creates a lot of waste. Our assembly line approach could save both time and money by allowing you to do all of these reactions at the same time in a single reactor.”
In addition to synthesizing drugs, scientists have also developed methods for using bacteria to grow specific molecules very rapidly. Though this method produces quick results, scientists are limited in their ability to design the molecule properly. This often forces the chemical to have a limited use in pharmaceuticals because it is just too broad to be of any major use.
“We want to have the molecule walk along an assembly line that we have designed to provide the specific compound of interest,” Michaelis said. “In this way we can generate really complex molecules, as nature would make, but without having to perform many chemical steps individually.”
Michaelis and his team have focused on this problem of creating antimicrobial compounds and have started developing the assembly line approach with nature as an inspiration.
“Drug developers often look to nature for inspiration of the types of compounds that would make good drugs.” Michaelis said. “We are looking to nature to teach us how to synthesize those compounds efficiently so that we can use them as drugs.”
One of the major challenges associated with developing new drugs for tuberculosis or malaria is that the people that could benefit the most from these new drugs are also some of the world’s poorest populations. The Michaelis lab wants to dramatically reduce the cost of developing and synthesizing new drugs.
“In a proposal that I wrote, we have taken an anti-malarial compound that somebody made—it took them seventeen different chemical reactions to make this molecule—and based on this idea, we were able to propose a 6-step synthesis,” Michaelis said. “So we have made a significant reduction, but we want to go much further than that. We want to perform all six steps on our assembly line, in a single reactor, so that we can put in all the starting materials and come back the next day and have our compound.”