Sallyport - The Magazine of Rice University - Winter 2002

Segura Secures Schlumberger Fellowship - Students
Winter 2002
VOL.58, NO.2
Segura Secures Schlumberger Fellowship
Mike Segura’s goal of developing enzymes that make new natural
products has earned him this year’s Schlumberger Foundation
Fellowship.
Segura, a graduate student in the Department of Chemistry, is studying how
plants make triterpenes—compounds that are useful for medicinal and
agricultural applications. He’s trying to determine how synthases, or
enzymes, that make triterpenes form their complicated structures. By
changing the sequence of amino acids in these triterpene synthases, Segura
can make new compounds with different properties.
“The reactions that triterpene synthases catalyze are so complicated that
chemists can’t do them without enzymes, and the best way to make new
triterpenes is to develop new triterpene synthases,” said Segura, whose
fourth year of graduate study at Rice is being supported by the 2001–02
Schlumberger Foundation Fellowship.
Mike Segura
The fellowship is awarded each year to a student in the Wiess School of
Natural Sciences in mathematics, earth science, chemistry, or physics. Dean
Kathleen Matthews selected Segura from the students nominated by the
department chairs in natural sciences. Schlumberger Ltd., the secondlargest
provider of oil-field services, funds the fellowship through a
charitable foundation it established in New York City.
Segura’s approach has been to make large pools of mutant triterpene
synthases and then identify individual mutants that make the desired
compound. One such compound is lanosterol, a steroid that yeast needs to
make cell membranes. Another is cycloartenol, a very complex molecule
that is found only in plants and that is required for plant growth.
Segura found that a mutant of the enzyme that normally makes cycloartenol
can make lanosterol using a technique called genetic selection. He put
thousands of mutant cycloartenol synthases into a yeast strain that needs
lanosterol to live. These strains were then grown without lanosterol, and
only those that acquired an enzyme that can make lanosterol lived. Because
only the yeast that can make lanosterol thrived, Segura was able to sort the
randomly generated mutant genes to find amino acid combinations
necessary to make lanosterol. Segura found the catalytic amino acid that
caused the difference by DNA sequencing. He is mutating this amino acid
further to make other compounds.
In a more complicated method, Segura uses a technique known as “DNA
shuffling” to fragment two genes that perform different reactions, mix the
fragments, and recombine them into millions of randomly generated DNA
combinations. Segura is looking for enzymes that make lanosterol using the
same genetic selection system as before. “We created a new way to get
yeast to grow on cycloartenol, which is a nonnatural compound to yeast
since it is made in plants,” Segura said. Using this engineered yeast strain,
he can genetically select mutant triterpene synthases that make
cycloartenol, even though normal yeast can’t use cycloartenol for anything.
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