NEWS OF THE WEEK HOST-GUEST COOPERATION Patellamide A, originally isolated from the sea squirt Lissoclinum patella (below), is actually made by the symbiotic bacteria that the marine invertebrate harbors. Now, Escherichia coli can make it, too.
CLIMATE
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SOURCING MARINE NATURAL PRODUCTS E. coli delivers marine natural product from genes of symbiotic bacteria
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HE BIOSYNTHETIC GENES
for certain bioactive peptides have been isolated from bacteria living symbiotically in sea squirts and expressed in Escherichia coli, according to a new study. The work offers a sustainable way to supply marine natural products for human use. Many marine natural products are potentially therapeutic. The true source of these bioactive compounds, however, has been hotly debated, says William Fenical of Scripps Institution of Oceanography On the basis of structures, scientists have suspected that bioactive compounds from marine inver-
tebrates are made by the symbiotic bacteria they harbor. Last year, two groups identified bacterial symbiont genes likely to be responsible for polyketides in a marine sponge (Proc. Natl Acad Sci. USA 2 0 0 4 , 1 0 1 , 16222) and for bryostatins in a marine bryozoan (Chem. Biol 2004,11,1543). The researchers did not settle the issue of source because they did not show that the genes lead to the natural products. AsJon Clardy ofHarvard Medical School puts it, "Looking at a gene sequence doesn't put compounds in a bottle." Now, for the cytotoxic cyclic peptides called patellamides, Eric W Schmidt at the University of Utah; Jacques Ravel at the Institute for Genomic Research, Rockville, Md.; and coworkers have taken the next step to pinpoint the source. After identifying the biosynthetic genes from the genome ofProchloron didemni, which is the
CHANGE
Investors Pledge Funds For Clean Technologies t a United Nations-sponsored meeting on May 10, more than two dozen leading U.S. and European institutional investors, managing more than $3 trillion in assets, pledged to invest $1 billion in technologies that would help reduce greenhouse gas emissions. They also called on U.S. companies to release information about the financial risks they face from climate change. The investors said that, because climate change will have a far-reaching impact on the global economy, there is a strong need for companies to address the issue. They released a 10-point action plan, in which they commit to ranking the world's 100 largest companies on their plans to tackle global warming. They also say they will urge the U.S. Securities & Ex-
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change Commission to require firms to disclose financial risks related to climate change. "Corporate and financial leaders need to look strategically at climate change and how it will impact the long-term health of businesses, industries, and our economy," said Connecticut State Treasurer Denise L Nappier, one of the 26 investors behind the action plan. Investors can benefit from opportunities, such as wind farms, that are becoming profitable as greenhouse gas limits are enacted around the world, she said. The UN meeting was attended by more than 375 leaders in the financial and corporate world, including seven state treasurers and the heads of 10 large pension funds. It was sponsored by the investor group CERES and the UN Foundation.-BETTE HILEMAN
bacterial symbiont ofthe sea squirt Lissoclinumpatella, they cloned the genes and inserted them in is. coli, which produced the expected compounds (Proc. Natl Acad. Sci. USA 2005,102,7315). The work is the first "to establish that the small molecule is really made by the symbiotic microbe," Clardy says. Major efforts have been undertaken to produce marine natural products synthetically given that supplies are limited and difficult to sustain, he explains. "Now, we're inching closer to a good supply source by culturing and not by synthesis," he adds. Fenical—as well as David J. Newman of the National Cancer Institute—tells C&EN that sci-
Patellamide A
entists in Australia and the U.K. disclosed similar results last November at a meeting of the Society for Industrial Microbiology in San Diego. Team member Marcel Jaspars of the University of Aberdeen, Scotland, says they used shotgun cloning to express the patellamide genes in E. coli, whereas Schmidt and colleagues used a deliberate approach. "Our next step was to be the sequencing of the producing clones, which would have led us to the same conclusions" as in the PNAS paper, Jaspars says. "We have not yet been successful in publishing our work," he adds. Meanwhile, Schmidt's lab is continuing to improve the harvest ofpatellamides fromls. coli to support a slew of experiments Schmidt is eager to do. At the top of his list, he says, is testing the flexibility of the biosynthetic pathway —MAUREEN R0UHI WWW.CEN-ONLINE.ORG
