BIOCHEMISTRY
Enzyme coordinates pericyclic trifecta LepI catalyzes three concerted rearrangements on paths to the natural insecticide leporin C Pericyclic reactions, in which electrons move in concert to rearrange a molecule’s structure, are standard tools for synthetic chemists. But examples of such transformations in nature are fairly rare. Chemists have now identified an enzyme that catalyzes three pericyclic reactions in the biochemical pathway that produces the fungal natural product leporin C. “This really opens up the idea that nature is able to affect reactions of much broader generality than we ever knew before,” says Kendall N. Houk, a University of California, Los Angeles, chemistry professor who led the study along with UCLA’s Yi Tang and University of Shizuoka’s Kenji Watanabe. The enzyme, called LepI, begins by dehydrating a leporin precursor to generate a reactive intermediate. This intermediate, with the help of LepI, can either undergo a hetero-Diels-Alder reaction to produce the desired compound leporin C, or it can perform an intramolecular Diels-Alder reaction to produce a different intermediate that is then subject to a retro-Claisen rearrangement to produce leporin C (Nature
H
O 2017, DOI: 10.1038/nature23882). H Diels-Alder When used by synthetic chemists, these Ph NH O pericyclic transformations often have to be performed at high temperatures, Tang notes. Also, he points out, it can be difRetro-Claisen O rearrangement ficult to control the products’ regio- and Ph stereochemistry. “As with any biocatalyst, Heterothis enzyme has potential to be engiDiels-Alder N O neered to catalyze such reactions under H mild conditions with selective product H Ph = phenyl formation,” Tang says. He also points out O that leporins are deadly to insects, so this LepI catalyzes three Ph enzyme’s chemistry could lead to selective pericyclic reactions H and potent insecticides via either synthesis shown to make leporin N O of novel leporin analogs or large-scale bioC. H engineered production of native leporins. Leporin C that catalyze unusual LepI is also noteworthy because the enzyme uses S-adenosyl-l-methionine (SAM) transformations of the carbon skeletons in their substrates rather in an unexpected manner. SAM generally than conventional methylation reactions,” transfers methyl groups to substrates. But based on computational work, the chemists comments Hung-wen (Ben) Liu, an expert speculate that in LepI, SAM’s methyl group, in enzyme mechanisms at the University of Texas, Austin. which is adjacent to a positively charged The chemists are currently using cryssulfur, is acting as a hydrogen-bond donor tallographic techniques to find definitive to catalyze the pericyclic transformations. experimental evidence for what SAM does “This places LepI on a short but growin LepI.—BETHANY HALFORD ing list of methyltransferase homologs
AWARDS
C R E D I T: U TEXAS , AUST I N
Goodenough wins 2017 Welch Award At an age when most people have long stopped working, John B. Goodenough, 95, is still going strong. Goodenough, who holds the Virginia H. Cockrell Centennial Chair in Engineering at the University of Texas, Austin, is recognized worldwide as the inventor of the commercially successful rechargeable lithium-ion battery—the
workhorse that powers most portable electronic devices as well as electric automobiles. For his “contributions to chemistry and humankind,” the battery pioneer will receive the 2017 Robert A. Welch Award in Chemistry and $500,000 in prize money. Through research conducted in the late 1970s and early 1980s, Goodenough demonstrated that lithium cobalt oxide could serve as the cathode in a long-lived rechargeable battery that packed a lot of energy into a small, lightweight package. Coupled with a lithium-intercalated graphite anode, Goodenough’s battery was a hit with manufacturers of portable electronic devices. The Texas researcher continues to investigate battery materials, probing their structures and electronic properties in addition to the electrochemical and solid-state chemical reactions they undergo.
Earlier this year, for example, Goodenough and coworkers reported that encasing the ceramic electrolyte layer in a sodium-ion battery with a thin polymer film impeded unwanted, dangerous electrochemical reactions. The hazards associated with those reactions have slowed development of rechargeable sodium-ion batteries, which could offer a less expensive alternative to lithium-ion batteries. “There’s no more fitting candidate for this award,” says Clare P. Grey, a rechargeable battery specialist at the University of Cambridge. Grey, who took courses taught by Goodenough when she was an undergraduate at the University of Oxford, notes that Goodenough conducted seminal work in many fields, including fuel-cell materials and magnetism. Grey adds, “John has been an inspiration to all of us.”—MITCH JACOBY SEPTEMBER 18, 2017 | CEN.ACS.ORG | C&EN
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