NEWS OF THE WEEK
FINDING THE KEY TO MORPHINE
module, a cytochrome P450, oxidizes (S)-reticuline to form 1,2-dehydroreticuline. The other module, an oxidoreductase, converts that product into (R)-reticuline. The new protein brings the idea of bioengineered morphine closer to reality. Identifying the STORR PLANT BIOLOGY: Fusion protein paves protein makes microbial production of morphine feaway to making opioids in microbes sible, says Hiromichi Minami, a bacterial engineer at Ishikawa Prefectural University, in Japan, who was not involved in the study. or years, researchers have been unable to identify To find the missing enzyme, Graham’s team identian enzyme that the opium poppy Papaver somfied mutant poppy plants that accumulate (S)-reticniferum uses to synthesize morphine. Without uline instead of making morphinans. The researchers the enzyme, which sits in the middle of the plant’s guessed that these plants probably had faulty versions biosynthetic pathway and converts the intermediate of the enzyme they were looking for. (S)-reticuline into (R)-reticuline, poppies can’t make Ultimately, they fished the gene for the unknown morphine or related opioid compounds, known collecenzyme out of a library of genes expressed in poppies. To A fusion protein tively as morphinans. do so, they used as bait a short fragment of RNA that inwith two modules Now a team led by Ian A. Graham of the University terferes with another enzyme in the morphine pathway catalyzes the (S)of York, in England, has finally identified that protein, with a similar sequence. They then sequenced the same to-(R)-reticuline which they call STORR, for (S)-to-(R)-reticuline (Scigene from three mutants and found it to be disrupted. conversion ence 2015, DOI: 10.1126/science.aab1852). STORR turns As a plant scientist, Graham plans to use the informain morphine biosynthesis. out to be a fusion of two enzyme modules. The first tion about the discovered fusion protein to help pharmaceutical firm GlaxoSmithKline improve poppy CH3O CH3O CH3O plants grown commercially for various alkaloids. + “This was the last remaining step to be described NCH3 Cytochrome P450 NCH3 Oxidoreductase NCH3 HO HO HO module module H for synthesis of morphinans,” says Vincent J. J. H HO HO HO Martin, a synthetic biology researcher at Concordia University, in Montreal, who has been working on CH3O CH3O CH3O engineering yeast to make various alkaloids. “Now (S)-Reticuline 1,2-Dehydroreticuline (R)-Reticuline the story is complete.”—CELIA ARNAUD
F
HOUSE CLEARS CHEMICALS BILL CONGRESS: Senate expected to
Shimkus
U.S. CONGR ESS
vote on reform of commercial substance law in coming weeks
I
N A STRONG BIPARTISAN SHOWING, the U.S.
House of Representatives on June 23 passed legislation that would overhaul how commercial chemicals are regulated. Lawmakers approved the bill, which would update the 1976 Toxic Substances Control Act (TSCA), voting 398-1. The proposed TSCA Modernization Act of 2015 (H.R. 2576) would change how thousands of chemicals that are already on the market are controlled. It would, however, leave in place existing rules for approving new substances. It also would give the Environmental Protection Agency sweeping new authority to ask chemical makers for safety data if the agency finds a substance poses a risk to human health or the environment. But some environmental activists are questioning whether EPA can determine that a chemical poses a risk if it lacks safety data. CEN.ACS.ORG
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H.R. 2576, introduced by Rep. John M. Shimkus (RIll.), is more narrowly targeted than a Senate bill to revise TSCA (S. 697), introduced by Sens. David B. Vitter (R-La.) and Tom S. Udall (D-N.M.). Notably, the House bill omits controversial provisions found in S. 697 that would override state chemical laws. Preemption of these state statutes, which has been a goal of the chemical industry, remains a sticking point that the House and Senate will have to hash out. The chemical sector is applauding passage of H.R. 2576 and urging the Senate to act quickly. “Congress can deliver a much-needed update to TSCA as well as a major environmental and commercial policy accomplishment to the President’s desk for his signature this year,” says Calvin M. Dooley, president and chief executive officer of the American Chemistry Council, an industry group. Many environmental groups back TSCA reform, but they are particularly worried about a provision in the House bill that would allow manufacturers to pay for EPA safety reviews of chemicals that industry selects. This would shift the agency away from reviewing the riskiest substances on the market, activists argue. “It tips much too far in favor of an industry in serious need of regulation,” says Ken Cook, president and cofounder of the Environmental Working Group. The Senate is expected to vote on S. 697 in coming weeks.—BRITT ERICKSON
JUNE 29, 2015
