Could the answers to humanity’s greatest ails grow just beneath our feet, lying dormant in the cells of biological organisms? Some naturally occurring plants may contain cures for diseases, keys to alternative energy, and more. In tweaking the chemical pathways of some organisms, biologists can produce compounds that are unmatched by synthetic methods and relevant to pressing problems.
Distinguished McKnight Professor Claudia Schmidt-Dannert is an expert in the field of metabolic pathways and natural product biosynthesis, and is experimenting with cutting and pasting genes from unrelated organisms to produce novel pathways never before seen in nature. These carefully designed pathways have proven instrumental to the discovery of more effective, less expensive pharmaceuticals.
Tapping natural products
Professor Schmidt-Dannert works at the interface of biochemistry, genomics, biotechnology, engineering, chemistry and microbiology. She identifies genes in unrelated microorganisms and synthetically combines them into a single organism, using molecular biological techniques. Employing special tools, she engineers novel enzymes to create unique compounds that have a wide range of biological functions and are of interest as drugs, antioxidants, colorants, vitamins and aroma compounds.
Scientists are now working together, across the globe, to sequence the DNA of thousands of organisms. But according to Schmidt-Dannert, understanding these networks of genes does not necessarily allow scientists to manufacture new pathways.
“Sometimes cells just don’t do what you want them to do, and they are surprisingly robust,” Schmidt-Dannert says. “When you think about changing this and that, cells have a solution to outsmart you.”
Probing the lowly mushroom
Mushrooms are a largely untapped source of natural products with potential medicinal properties. Schmidt-Dannert’s lab has sequenced the genome of the “Jack O’Lantern” mushroom, which contains chemicals with anti-cancer properties. Her team has identified the organism’s natural product pathways, and is stringing them together in the hopes of creating new bioactive compounds.
“The goal is to introduce biosynthetic functionalities taken from mushrooms into genetically engineerable microorganisms such as E. coli or yeasts,” she says. “My hope is to design microbial cells to become little factories.”
Although Schmidt-Dannert is the first biologist to investigate the biosynthetic properties of the Jack O’ Lantern mushroom on a gene level, she’s hardly the first to discover that mushrooms contain diverse sesquiterpene compounds, which are a rich source for the discovery of new pharmaceuticals. This compound has demonstrated antimicrobial, cytotoxic, immunomodulating and anti-inflammatory activities, and has been employed in drugs that battle cancer and malaria.
When asked about the rapidly changing landscape of biotechnology, Schmidt-Dannert points to the following trends:
Engineers lend expertise: Biologists are thinking more and more about how to implement new networks into cells. Rather than designing one pathway, step by step, researchers are thinking about how to integrate these foreign pathways or constructs into a cell using engineering principles.
Biologists break out of the niche: Moving forward, there will be no single discipline in biology. The field is becoming more multidisciplinary and interdisciplinary. Soon, there will be no biochemistry and microbiology; biologists will need expertise in a variety of fields.
Biotech is booming: As the discipline tackles increasingly diverse and dynamic scientific problems, students are taking notice. At the U of M, the biochemistry major is the largest departmentally based major in the College of Biological Sciences, with 345 undergraduates enrolled.