NEWS OF THE W EEK
A CATALYTIC FIRST ENZYMOLOGY: Bacteria master reaction
by making the substrate a radical
A
COMMON ANAEROBIC MICROBE in the hu-
man gut has been caught doing some curious biochemistry that had been previously postulated but never proven. Clostridium difficile has an enzyme that pulls off a difficult reaction needed for energy metabolism by turning its substrate directly into a radical, a new report shows (Nature, DOI: 10.38/nature06637). Typically, substrate radicals involved in enzyme-catalyzed reactions are generated through radical organic cofactors or active-site amino acids. C. difficile provides the first case in which an enzyme radicalizes its sub-
RADICALIZED Recalcitrant hydroxyacyl-Coenzyme A is forced to lose a water molecule by being made its own radical. R is Coenzyme A. H H
O– H H
e–
RS •
RS HO
HO
H
H2O
O–
H •
RS H
H
Ketyl radical
Allylic ketyl radical
EPA SETS STRICTER OZONE STANDARD AIR POLLUTION: Chemical manufacturers say change is unnecessary and too costly
New ozone standard may help reduce smog that plagues cities like Los Angeles.
T
HE ENVIRONMENTAL Protection Agency is tightening the national air quality standard for ground-level ozone from 0.08 parts per million to 0.075 ppm. This concentration is still less stringent than what many experts contend is required to protect public health and prevent premature deaths. “America’s air is cleaner today than it was a generation ago,” EPA Administrator Stephen L. Johnson noted when announcing the new standard on March 12. “By meeting the requirement of the Clean Air Act and strengthening the national standard for ozone, EPA is keeping our clean air progress moving forward.” Johnson said the agency based SHUTT ERSTOCK
© 2008 NATURE
O
WWW.C E N- ONLI NE .ORG
12
strate directly via simple electron transfer, comments Joseph T. Jarrett, a chemist at the University of Hawaii, Manoa, in an associated commentary in Nature. The team of researchers, led by Antonio J. Pierik, a biochemist at Philipps University in Marburg, Germany, also shows that the substrate radical is produced through a reduction reaction rather than an oxidation, contrary to standard textbook redox activation. “Most enzymes that are known to generate radicals do so by removing a hydrogen atom from the substrate,” Jarrett notes. The unusual C. difficile reaction is undertaken by an enzyme called 2-hydroxyisocaproyl-CoA dehydratase, which converts leucine into short-chain fatty acids. Metabolizing leucine in the absence of oxygen is difficult, partially because midway through the process a stalwart 2-hydroxyacyl-CoA intermediate is created. This 2-hydroxyacyl-CoA cannot be reduced further until it can shake off a water molecule. That’s when the dehydratase steps in. Using an electron from the iron-sulfur clusters in its active site, the enzyme turns the 2-hydroxyacyl-CoA into a ketyl radical that can shed the crucial water. The radical product is oxidized to give an isocaprenoyl derivative that can then be further reduced. “Time will tell whether this newly discovered radical mechanism is used by other enzymes,” Jarrett notes. “But the authors have shown that even in the relatively mature field of enzymology, there is still much to learn.”—SARAH EVERTS
its decision on the most recent scientific evidence about the effects of ozone, the primary component of smog. The change means that the air in 345 U.S. counties will violate federal standards, four times the current number of violators. The American Chemistry Council, which represents 134 major chemical manufacturers, believes the 0.08ppm limit sufficiently protects public health and is based on sound scientific information. “The available science is largely unchanged since the 1997 standard was issued and demonstrates that there is no clear and substantial basis for making the standard stricter at this time,” ACC said in a statement. Lowering the ozone standard “unnecessarily will impose significant new burdens on states and others even as they continue to try and comply with the 1997 standard.” In contrast, the American Lung Association has called for a much stricter standard, as have more than a dozen other public health and medical societies. In 2006, EPA’s Clean Air Scientific Advisory Committee said a standard of between 0.060 and 0.070 ppm is needed to provide an adequate margin of protection for millions of people susceptible to respiratory illnesses. Business groups waged an intense lobbying campaign to preserve the old standard. In meetings with EPA and White House officials, they argued that the estimated $8.5 billion annual cost of meeting a lower limit could hurt the economy.—GLENN HESS
M ARC H 17, 20 0 8
