Natural Products
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Organic molecules produced naturally by biological entities, such as bacteria, invertebrates, plants, and higher forms of life are called Natural Products. A majority of clinically used antibiotics and drugs are derived from Natural Products. With antibiotic resistance on the rise, the medicinal chemists are turning their attention to Natural Products to keep up the supply of new pharmaceuticals to treat human disease. There is an urgent need to find new Natural Products, diversify their chemical structures to tailor their medicinal chemistry properties, and understand how they modulate biological outcomes.
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Nature uses enzymes to fashion simple biochemical building blocks into highly complex Natural Product structures. These enzymes, in turn, are encoded by genes organized into biosynthetic gene clusters. Click on the gallery below for an overview of how we think about Natural Product biosynthesis and the kinds of questions that motivate our research.
Constructing Natural Products
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In Nature, organic molecules are constructed using enzymes coded by genes in a Natural Product producer plant, bacterium, or any other biological source. Thus, in theory, by finding these genes, we can construct Natural Products in the lab. However, this problem becomes hard to solve when the biological complexity of the Natural Product source gets too high, such as in marine sponges (pictures on the right) where thousands of bacteria, fungi, and viruses live in a symbiotic community within the eukaryotic host. In such cases, genes and enzymes that construct the Natural Product become very hard to find.
We reverse engineer the process by which a Natural Product can be constructed. Then, we use this information to 'mine' metagenomic datasets to find enzyme candidates that can fulfill the requisite chemical roles to construct the Natural Product. Using biochemical techniques, we then ask whether the enzyme candidates can really catalyze the reactions that we hypothesized? This process involves numerous biochemical and synthetic biology experiments. Browse Open Positions for creative chemists, biochemists, chemical ecologists, and chemical oceanographers to explore marine sponge derived Natural Products. |
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Biochemistry and Structural Biology
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Natural Product biosynthesis is Nature's tinkering ground when it comes to developing new enzymatic reactions. Biological reactions in the lab are characterized using a variety of biochemical techniques to discover novel enzymatic biochemistry.
A core interest of the lab is to generate three dimensional, high resolution structures of Natural Product biosynthetic enzymes in complex with their cofactors, substrates, and inhibitors using X-ray crystallography. We then use these crystal structures to rationally engineer enzymes for tailored biotechnological applications. Enzymological biochemistry in the lab is supported by organic synthesis of substrates and product standards, and chemical derivatization of natural products. Browse Open Positions for biochemists, structural biologists, and analytical and synthetic chemists. |
Analytical Chemistry, Mass Spectrometry
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How do we find new natural products? How do we find molecules that might serve important biological roles in their ecosystems? By using mass spectrometry, we inventory bio- and chemodiversity hot spots of the world to enable a community effort for inventorying Natural Product chemistry.
We are using high resolution tandem mass spectrometry, molecular networking, and next generation DNA sequencing in a pilot experiment to inventory marine Natural Product chemistry from the Indo-Pacific island of Guam. In collaboration with other faculty at Georgia Tech and elsewhere, these efforts are envisaged to be expanded to other sites in the world. Browse Open Positions for analytical and synthetic chemists, chemical ecologists, and 'big-data' enthusiasts. |
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