‘It’s Like Speeding Up the Process of Evolution’

How can production of common items be made more efficient and sustainable? The answer may lie in the science of metabolism.

 |  Transcript [PDF]

From the yeast used to make bread dough rise, to the cells grown in bioreactors to make pharmaceuticals like insulin, humans take advantage of the metabolism of living things to make all kinds of products. And it’s getting easier than ever to manipulate cells to maximize the products we want.

Biochemist Krishna Mahadevan, professor of chemical engineering at the University of Toronto, studies the science of metabolism to make it easier to know where to start.

Metabolism is a critical activity for all living things. Through metabolism, all cells convert food into energy and the molecular building blocks of life. That means that for every gram of food consumed, only a fraction of that starting material will be converted into the desired product.

But understanding which biochemical pathways that lead to that product, and which are unnecessary and lead elsewhere, could help boost productivity. It’s the first step in making educated adjustments to cellular metabolism.

“The thing that’s really interesting for us is the ability to actually write genomes,” says Mahadevan. “It’s the idea of genome editing. That will allow us to program biology just the way you program computers. And that is almost like speeding up the process of evolution.”

Take, for instance, a bacterial cell being put to work making ethanol. Understanding metabolism would be the first step in knowing which genes to turn up to increase ethanol production, and which to turn down to reduce unnecessary by-products.

“Understanding which pathways contribute to ethanol and which pathways contribute to the rest of the cell’s metabolism is important, because it will help me figure out, in a targeted way, which components to play around with or change,” says Mahadevan.

Currently, Mahadevan is working on making the building blocks for nylon in a more sustainable way. Nylon is a material that is used in many textiles and building materials, from clothing, to upholstery, to countertops, and more. Despite being used in so many common products, nylon is still made using an unsustainable process.

“Currently the nylon that’s made is made in a way which is highly energy intensive, and there’s a lot of potent greenhouse gas that’s emitted during this process,” explains Mahadevan.

“What we plan to do is replace this petrochemical waste process with a biological process where we will engineer the cells to spit out the nylon precursors. And that we’re trying to make from cellulosic sugars and so forth.”

Cellulosic sugars can be extracted from many sources, including the waste products of forestry and agriculture like bark and corn cobs. This technology would provide a sustainable alternative for so many of the products we use every day.

“So that’s the idea,” adds Mahadevan. “It keeps me up at night, I think about how we can solve the problems, optimize it in such a way that it becomes a commercial reality.”

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Krishna Mahadevan is a professor in the Departments of Chemical Engineering & Applied Chemistry, and Institute of Biomaterials and Biomedical Engineering at the University of Toronto. He obtained his BTech from Indian Institute of Technology, Madras in Chemical Engineering in 1997 and then obtained his PhD from the University of Delaware in Chemical Engineering in 2002.

He was a research scientist at Genomatica Inc., San Diego from 2002–06 and has also held appointments as a visiting scholar and a guest lecturer at the Department of Bioengineering in the University of California, San Diego, and in the Department of Microbiology, University of Massachusetts, Amherst.

His research interests are in the area of modeling, analysis and optimization of metabolism for applications in bioremediation, biochemicals production and medicine and has published over 100 articles in these areas. He has received David W. Smith Jr. Best Paper Award in 2006, the Jay Bailey Young Investigator Award in Metabolic Engineering in 2010, the Society of Industrial Microbiology and Biotechnology’s Young Investigator Award in 2012, University of Toronto FASE Research Leaders Award in 2013, the Alexander von Humboldt Fellowship in 2014, the Syncrude Innovation Award in 2014, and Biochemical Engineering Journal Young Investigator award in 2017.

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