Sherlock Holmes never solved mysteries like the nature-made ones that have challenged Ian Scott for decades.

Scott, who holds the title of Distinguished Professor of Chemistry and is director of the Center for Biological Nuclear Magnetic Resonance at Texas A&M University, has devoted more than 30 years of his career to solving some of nature's mysteries, including the blueprint for the synthesis of vitamin B12 and the anti-tumor drug taxol.

"We have to put the pieces of the puzzle together to find out how nature builds these complicated molecules from very simple building blocks," Scott says.

An enormously complicated molecule with an unusual cobalt atom in the center, vitamin B12 is essential for human health. A shortage of the vitamin leads to pernicious anemia, a condition that is often fatal if left untreated.

Bacteria produce vitamin B12 naturally and though pharmaceutical companies produce large quantities of synthetic B12 each year, Scott's work is expected to improve the process, making the vitamin even easier to produce.

"We can reconstruct the whole pathway in the test tube without having to wait for a plant or a bacterium to grow," the Texas A&M researcher says. "It's like speeding up the natural process."

Scott used molecular biology and organic chemistry techniques in combination with nuclear magnetic resonance (NMR) spectroscopy to determine exactly how B12 is produced. Using genetically engineered bacteria, Scott hunted for the genes - all 22 of them - responsible for producing the vitamin. The DNA contained in those genes codes for the particular enzymes that synthesize B12.

"Once we've got the DNA," Scott says, "we can get the enzymes, and once we've got the enzymes we can begin to find out how they work and then put them back together in the test tube. Out comes the B12 structure.

"It really cuts down the number of weeks and months for these materials to be made if you can make them in the lab overnight, using this technique of mixing enzymes," Scott says.

Scott is applying the lessons learned from his work on vitamin B12 to the cancer drug taxol. Taxol, which comes from the Pacific yew tree, is a powerful therapy for some types of ovarian cancer. And though taxol is a simpler molecule than B12, Scott says it is still a challenge to find all the genes that make the drug.

"It's not so easy to work with plants as it is with bacteria," Scott says. "There are about 50,000 genes in the yew tree and we have to choose the 20 that make taxol. It's like hunting for the needle in the haystack."

Taxol is in rather short supply. Currently, the drug is made from the leaves of Pacific yew trees and though taxol can be produced synthetically, the 35-step process is not commercially viable, Scott says.

"We want to rescue the genes that make taxol and put them back together again so we can have a factory, if you like, for making it," Scott says, allowing for quicker and cheaper production of the drug.

For his work on vitamin B12 and taxol, Scott was named the co-recipient of the prestigious Robert A. Welch Award in Chemistry in May 2000.

Contact: Lesley V. Kriewald, (979) 845-4646, lvk@univrel.tamu.edu, or Ian Scott, (979) 845-3243, scott@mail.chem.tamu.edu.

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