Research
Research
Natural Product Biosynthesis
Many antibiotics, anti-tumor drugs and other pharmaceuticals are produced by bacteria, fungi or plants. Unfortunately, isolation of compounds from the environment can be an expensive and low yielding process. Furthermore, isolation procedures provide limited opportunities to modify the chemical and biological properties of the natural product.
Understanding the enzymes that catalyze natural product synthesis may enable production in more tractable host organisms and may also facilitate reprogramming of biosynthetic pathways to produce "unnatural" natural products with improved pharmacological activities.
Madagascar periwinkle cell suspension culture displaying alkaloid production.
Untapped Potential of Plant Alkaloids
Plants produce an enormous number of complex natural products such as vinblastine, morphine and taxol that are used clinically. Despite the importance of these compounds, many plant natural product pathways remain poorly understood due to the challenges associated with working with higher plants.
A major focus in our group is to use plants, plant cell culture and plant associated microorganisms to produce novel product structures, using molecular biology, biochemistry and synthetic organic chemistry to create transgenic plants and plant tissue capable of producing “unnatural products”.
Mechanistic Elucidation
Many of the biochemical transformations in alkaloid biosynthesis are poorly understood. Another focus of our group is elucidate and understand the chemistry of these enzymatic transformations.
Alkaloid producing plants undergoing transformation with a reengineered biosynthetic enzyme.
Crystal structure of an alkaloid biosynthetic enzyme (obtained by Joachim Stockigt’s group) used to elucidate the chemical mechanism of this enzyme, which catalyzes a Pictet Spengler reaction.
In the News...
Download report on periwinkle cell culture and RNAi in SciBX here:
Download perspective on synthetic biology and drug development here:
Download Boston Globe Article here:
Download report on engineered periwinkle cell cultures in SciBX here:
Download 2009 MIT Tech Talk Article here:
Chemists engineer plants to produce new compounds - MIT News Office.pdf
Download 2009 Chemical and Engineering News Concentrate here:
Download 2009 Medical News Today story here:
Download 2009 Chemical Week story here:
MIT Chemists Engineer Periwinkle Cells to Produce New Compounds __ Chemical Week.pdf
Download 2007 report on derivatization of alkaloids by clicking here:
Getting a handle on biosynthesis.pdf
Download 2006 Tech Talk article here:
Download 2006 Chemical and Engineering News Concentrate by clicking here:
Chemical & Engineering News_ Latest News - Periwinkle Yields Unnatural Natural Products.pdf
Download 2006 Innovations Report by clicking here:
Elucidating Natural Product Biosynthesis in Plants
A large scale project to obtain the transcriptomes of 14 medicinal plants is currently underway. Researchers from the University of Kentucky, Michigan State University, MIT, Iowa State University, OleMiss and Purdue University are part of this consortium. Metabolite profiling data of these plant tissues will also be performed, allowing us to build correlations between gene expression and metabolite production. This large scale database will provide a modern resource for understanding and elucidating medicinal plant natural product biosynthetic pathways. For more information, click here.
Vinblastine biosynthesis in C. roseus (Madagascar periwinkle), with the uncharacterized enzymatic steps highlighted.