Nature’s Tiny Chemists

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Searching for new drugs

In addition to penicillin, fungi have been the source for cholesterol-reducing statins, antifungal drugs, a medication used to treat multiple sclerosis, and an immunosuppressant that transplant patients sometimes take to ensure their bodies don’t reject a new organ.

But, Oberlies says, “There are no anti-cancer drugs derived from fungal metabolites – zero.” Not yet, anyway. In an application for a project funded by the National Cancer Institute that netted the lab $2.7 million in research funds for 15 years, Oberlies wrote, “We strive to change that.”

Drug discovery is hard.

In addition to finding something that successfully attacks cancer in humans, new drugs must overcome three other major barriers: supply, solubility, and patents. “With any natural product, a major problem is supply. This was a huge problem with taxol,” Oberlies says of the yew-based cancer drug. “But, we can grow fungi easily, we can ferment fungi. Penicillin costs pennies because of that.”

The second issue: many natural products don’t dissolve in water. “They just don’t go into saline that you can inject in someone’s arm,” Oberlies says. “But there are techniques to get around that.”

The third issue is patents. To do the research and testing required to take a new compound from just “potentially useful” to “proven to safely and effectively treat disease in humans,” companies invest billions of dollars and years of time. They need patents that allow them to reap the rewards from financially risky drug development research.

But natural compounds can’t be patented. So, they must be altered in some way to make them artificial. “Some of the development process is to make an analogue,” Oberlies explains. “You’ve made the natural product not natural – changed an atom, changed a side chain, to optimize certain properties, and you can suddenly

Training Ground

Energy for the Environment

The latest initiative that has grown out of Oberlies’ lab started with a chance question by another professor in a departmental meeting.

A few years ago, Oberlies’ doctoral student Zeinab Al Subeh made a presentation to the faculty – a part of the graduate student training process in the Department of Chemistry and Biochemistry. They nurture rich scientific discussions that can blossom into new discoveries.

Dr. Shabnam Hematian asked the student about the “redox potential” of the fungal-derived compounds she was studying. Al Subeh didn’t know the answer – it relates to how efficiently the compound moves electrons around. However, she took the opportunity to explore the subject with one of Hematian’s electrochemistry-focused graduate students.

That started a collaboration to explore the potential of fungal chemistry in applications related to the generation, storage, and transmission of electricity. The collaboration has now bloomed into a rich, cross-university, cross-disciplinary research initiative called NICER – Nature Inspired Collaborative Energy Research.

The highly collaborative effort was kickstarted by a $1.5 million Research Opportunities Initiative – ROI – grant from the N.C. General Assembly. It’s now led by Oberlies and UNCG’s Dr. Minjeong Kim, assistant professor and associate head of computer science.

Doctoral student Reema Al-Qiam is focused on the perylenequinone class of fungal compounds and their potential energy applications.

The Next Generation

Penicillin changed the world. It and subsequent antibiotics remade medicine – extending average human lifespans by decades and turning once-deadly infections into, in many cases, mere medical annoyances.

“All of that started with a scientist making an observation in his lab. It was then picked up by chemists who isolated the molecule and figured out its structure. Then, teams of scientists developed ways to supply it at scale,” Oberlies says.

“A single observation, in a single Petri dish, followed to completion creates an antibiotics revolution.” That’s why he considers his work with students his most important contribution. “If we don’t train the next generation of scientists, who will do those kinds of experiments for the next 100 years?”


Learn more about Dr. Nick Oberlies in our Senior Research Excellence Award Winner interview

Story by Mark Tosczak
Photography by Sean Norona and David Lee Row

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