NEWS OF THE WEEK
MULTITASKING CATALYSTS BIOSYNTHESIS: Mix-and-match enzymes can catalyze all four isoprenoid coupling reactions
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NZYMES MADE OF BITS and pieces of two other enzymes can catalyze all four reactions used to build the skeletons of isoprenoid natural products, chemists have discovered. The multitasking catalysts may yield clues about how nature evolved the ability to make these compounds. Isoprenoids are the most chemically diverse fam-
M U L T I P L E C H O I C E Isoprenoid skeletons are made from two simple precursors via four coupling reactions.
PPO = diphosphate R = Isoprenoid group
ily of natural products. More than 55,000 naturally occurring isoprenoids or terpenoids are known, with examples from all over the world. This broad family includes compounds that play important roles in metabolism and cell structure. Remarkably, this vast array of compounds is generated from simple precursors by a set of just four coupling reactions: chain elongation, cyclopropanation, branching, and cyclobutanation. In nature, each reaction is usually carried out by a separate enzyme. In the course of studying these enzymes, chemistry professor G. Dale Poulter and coworkers at the University of Utah have created chimeras that can perform all four reactions (Science 2007,316,73). Starting with the chain elongation and cyclopropanation enzymes from a sagebrush plant, they replaced segments of the active site of the chain elongation enzyme with corresponding bits from the cyclopropanation enzyme. "We're not changing the size of the protein, and we're not introducing extra active sites," Poulter says. "All we're doing is changing the amino acids used to construct the active site." The unexpected discovery that some of the chimeras can perform all four of the coupling reactions could provide insight into how the natural enzymes that catalyze these reactions could have evolved from a single precursor. "Once you have the ability to do all four reactions, then making one pathway selective over another is basically what the job of evolution is about," Poulter says. The efficiency of the multitasking enzymes for the various reactions was dramatically different, he notes. In an accompanying commentary, David W. Christianson, a chemistry professor at the University of Pennsylvania, writes that the "chimeras exhibit remarkable trends in biosynthetic versatility." In addition, the work provides "compelling evidence" that the enzymes "that catalyze these fundamental coupling reactions diverged from a common ancestor early in the evolution of terpenoid biosynthesis," Christianson writes.—CELIA ARNAUD
COLLABORATION Companies team up with schools for education and R&D Sasol and AstraZeneca, two companies at opposite ends of the chemical enterprise and the globe, are joining with universities to help ensure a sustainable supply of trained researchers and engineers. The South African chemical company Sasol says it will invest $35 million over the next eight years to establish teaching and research capacity in chemistry and chemical engineering at selected South African universities. "The realization that our South African universities may not be able to fully pro-
vide Sasol's future manpower needs has resulted in us helping build strategic capacity through a university collaboration program," says Sasol Executive Director Nolitha Fakude. Meanwhile, the Anglo-Swedish pharmaceutical company AstraZeneca is working with the U.K.'s University of Nottingham to single out potential medicines of the future. The work builds on a joint doctoral training center set up at the university last year and sponsored by AstraZeneca and the British government's Engineering
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& Physical Sciences Research Council. The $5 million center is training 25 British pharmacy Ph.D. students over the next five years in targeted therapeutics. Teams from the company and the school recently got together at an "ideas generation" event to identify new areas for research on various diseases. Amanda Zeffman, project officer at Nottingham, says the event was one of the first such meetings to take place in the U.K. between academics and scientists from industry.-PATRICIA SHORT
