As a pioneer in the field of engineered biosynthesis, Chaitan Khosla—a chemical engineer at Stanford University—might seem like an unconventional choice for an Arthur C. Cope Scholar Award, which was established to recognize and encourage excellence in the area of organic chemistry. But Khosla's recognition demonstrates organic chemistry's breadth, as well as the similarities all chemists face when they set out to construct a complex natural product, whether they're building it in a round-bottom flask or assembling it with an enzyme, as Khosla does.
"I see what we do as being very much analogous to the way many of my synthetic colleagues see what they do," Khosla says. "A synthetic chemist thinks about the discovery of new chemistry, the mechanistic analysis of the fundamental principles that underlie that new chemistry, and the translation of this new chemistry into practical applications for making materials that couldn't have been made before or making materials that could have been made before with much greater difficulty in easier ways.
"Those three themes—discovery of new chemistry, understanding the mechanistic principles, and application of new chemistry—are the three pillars of our research programs," he continues. "We seek to discover new chemistry that exists in nature. We seek to understand the mechanistic underpinnings of that chemistry, and we seek to exploit that chemistry to practical ends. Conceptually you're doing the same things, you're trying to understand how bonds are made and broken and what's in it for the person on the street."
Currently, Khosla, 44, is the Wells H. Rauser & Harold M. Petiprin Professor of Engineering. He says his interest in nature's superior synthetic strategies for making polyketides was first piqued in his final years as a graduate student at California Institute of Technology. Enzymes and biocatalysts were once thought of as highly specialized systems, he explains. But by the early 1990s, he says, "it was becoming clear that the mega synthases that make complex antibiotics were very unusual in the sense that they were modular catalysts. You could think of them as the equivalent of the assembly lines for chemical catalysis."
He has spent his career trying to understand how this biological machinery works and how it can be made to make molecules. In doing so he's garnered an Arthur C. Cope Scholar Award "for his seminal contributions to understanding the mechanisms of polyketide biosynthesis and for the use of engineered biosynthesis for the production of new polyketides and therapeutic leads."
"Khosla has had a profound impact in chemistry, pioneering the emergence of the field of engineered biosynthesis and its application to the practical synthesis of natural and nonnatural products, including many drugs, therapeutic leads, and biological probes," says Paul A. Wender, Khosla's colleague at Stanford. "He has advanced our understanding of how nature's biosynthetic machinery can be engineered to synthesize natural and nonnatural products. This had changed how we think about many areas of synthesis and has equipped the modern synthetic chemist with a powerful and general tool to prepare therapeutic leads, materials, and novel structures."
Over the course of his career, Khosla has authored more than 230 papers. He holds more than 50 patents and is the founder of two biotech companies, Kosan Biosciences and Alvine Pharmaceuticals. "He has enabled the synthesis of more natural products than many make in a career and, in addition, has shown that by understanding the mechanisms of the biosynthesis machinery, one can assemble unnatural products with exceptional facility," Wender adds.
Although he has received numerous awards and achievements, Khosla says that he is proudest of his students. "They are the reason why I do what I do," he tells C&EN. "I've been blessed with many amazing students and I consider it a deep privilege to have a chance to engage them when they're at the beginning of their chemistry education and ride that wave with them as they go through and become world leaders."
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