Chemistry of Microorganisms and Microbial Communities

Understanding how microbes influence our health and the environment

The vast majority of living organisms are microbial. Estimates place the total number of microbes on Earth at 1030; for comparison, the human population numbers 7 x 109. The chemical transformations carried out by microorganisms influence human health, shape the environment, and produce medicinally important molecules. The recent rise in microbial genome sequencing has unveiled an unprecedented chance to understand the chemistry of the microbial world. Because of the outsized influence that microbial chemistry has on our lives and society, Prof. Emily Patricia Balskus, Associate Professor of Chemistry and Chemical Biology at Harvard University, is seizing this opportunity to discover, understand, and manipulate the chemistry of microorganisms and microbial communities. Leading an interdisciplinary team of scientists from around the world, Prof. Balskus is exploring multiple frontiers at the intersection of chemistry and microbiology. Her lab combines an understanding of enzyme mechanism with bioinformatics to rapidly identify new metabolic pathways in microbial genomes. They have discovered new enzymatic chemistry of biological importance as well as transformations that will inspire synthetic chemists and provide new tools for biocatalysis and biological engineering. Her group also studies the roles played by these new enzymatic reactions in host microbes and microbial communities, which will illuminate the importance of this chemistry in vivo. Additionally, Prof. Balskus is developing new approaches for manipulating chemical processes in individual microorganisms and the complex communities they inhabit. Ultimately, Prof. Balskus’ research will not only improve our fundamental understanding of the capabilities of these amazing organisms, but will also reveal new therapeutic strategies to treat a variety of human diseases and novel, greener ways to produce chemicals we rely on everyday.

Current research includes:

  • Exploring the Chemistry of the Human Microbiota: The microbial communities that live on and inside each of us are collectively known as the human microbiota, and the rapidly growing appreciation of the large influence our microbiota has on our well-being has been likened by scientists to suddenly discovering a new organ in the human body. However, our understanding of the molecular mechanisms underlying the biological impact of the microbiota is still extremely limited. By combining biochemical knowledge with bioinformatics, Prof. Balskus has uncovered pathways and enzymes that influence health and disease in the genomes of human-associated bacteria. Her team focuses on understanding gut microbial activities that have a demonstrated connection to human biology but are poorly understood from a genetic and biochemical perspective. Ultimately, their efforts will reveal how the chemical capabilities of the microbiota influence human health and provide new strategies for treating disease.
  • Manipulating Biological Function with Biocompatible Chemistry: Synthetic biologists use genetic techniques to modify bacteria to produce new, useful chemicals. This involves essentially hacking the bacteria, changing their DNA code to reprogram metabolism. This approach has limitations: there is no known code for carrying out some transformations, and some bacteria prove resistant to standard hacking techniques. Prof. Balskus is exploring a distinct, complementary approach to genetically manipulating microbial metabolism that she calls biocompatible chemistry. Biocompatible transformations are non-enzymatic chemical reactions that can interface with the metabolism of living systems in a way that alters how organisms function. Although developing these reactions is challenging due to the highly complex chemical environment required to support life, her group has been successful in expanding the scope of bacterial metabolism and increasing the size of the metabolic engineer’s toolbox. This research area intersects with Prof. Balskus’ microbiota research, which aims to discover molecules that inhibit disease pathways and manipulate microbial communities by “drugging” the microbiota, and has further applications in pollution treatment, toxicology, and energy production.
  • Unusual New Enzymes from Environmental Organisms: Prof. Balskus and her team are also working to discover new chemistry from microbial communities that can be used to make drugs and molecules. The field of biocatalysis, which uses enzymes (Nature’s catalysts) for non-natural chemical production, is providing more efficient ways to produce chemicals ranging from greener plastics to life-saving drugs. The major bottleneck preventing broader use of these biocatalysts is the limited number of reactions they are known to perform. Using an understanding of chemistry and biosynthetic logic, the Balskus lab is developing strategies that efficiently identify novel enzymes in the recently available wealth of microbial genome sequencing data. They focus on finding enzymatic pathways responsible for producing complex, biologically active molecules whose biosynthesis likely requires reactions unprecedented in traditional organic chemistry. By discovering novel enzymes and harnessing the diversity of microbial chemistry, Prof. Balskus is providing additional sources of reactivity that will change the way both synthetic chemists and metabolic engineers access important small molecules.

Bio

Professor Emily Balskus joined the Chemistry and Chemical Biology faculty of Harvard University in 2011. She is also an Associate Member of the Broad Institute of Harvard and MIT, is a Faculty Associate of the Microbial Sciences Initiative at Harvard, and is a member of the Harvard Digestive Diseases Institute. Emily’s independent research program has been recognized with multiple awards, including the 2011 Smith Family Award for Excellence in Biomedical Research, the 2012 NIH Director’s New Innovator Award, and the 2013 Packard Fellowship for Science and Engineering. She is also a 2012 Searle Scholar and was named one of MIT Technology Review’s 35 Innovators Under 35 for 2014.

As the child of two teachers, education has always been an integral part of her life. Growing up in Cincinnati, Ohio, Prof. Balskus was encouraged to pursue a career in science by her high school chemistry teacher and spent her high school summers teaching chemistry and biology to at-risk middle school students. She fell in love with research as an undergraduate at Williams College, spending summers in labs at Williams, Leiden University in the Netherlands, and The Ohio State University, as well as a year abroad at The University of Cambridge in the UK. She realized that she loved discovery-based research: developing new chemical reactions and devising new ways to access important molecules in the lab. She graduated from Williams College in 2002 as valedictorian with highest honors in chemistry.

As a graduate student in Chemistry at Harvard University, Prof. Balskus strengthened her expertise in chemical synthesis, but towards the end of this experience found herself drawn to biological questions. How do living organisms make molecules? What are the functions of small molecules in biological systems? To explore these questions she moved out of her comfort zone and pursued postdoctoral research at Harvard Medical School, studying how photosynthetic bacteria make small molecule sunscreens that protect them from UV radiation. This research experience opened her eyes to the tremendous chemical talents of microorganisms and the many important roles they play in shaping the environment. This interest led her to become curious about the chemistry of the microbial communities that live in and on humans—the human microbiota—which is now a major focus of her current research.

Prof. Balskus enjoys the challenge of multi-disciplinary research problems; often knowledge and perspectives from multiple fields are needed to tackle difficult questions. She is also motivated by the thrill involved in discovering something new and the possibility that her work might one day help lead to new treatments for human disease. She also understands and deeply appreciates the power of an educator to challenge and inspire students, and is honored to help teach and train the next generation of scientists.

In her spare time, she and her husband like to run with their retired greyhound and enjoy the arts and architecture.

For more information, scholar.harvard.edu/balskus/

Publications

Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme

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A prodrug mechanism is involved in colibactin biosynthesis and cytotoxicity

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Rescuing auxotrophic microorganisms with non-enzymatic chemistry

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A biocompatible hydrogenation merges organic synthesis with microbial metabolism

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Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut...

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Awards

NIH Director’s New Innovator Award, 2012

Packard Fellowship in Science and Engineering, 2013

Kavli Fellow, National Academy of Sciences, 2013

MIT Technology Review Innovator Under 35, 2014

Damon Runyon–Rachleff Innovation Award, 2014