NEWS OF THE WEEK CHEMICAL
BIOLOGY
GENOME MINING HITS PAY DIRT DNA sequence guides discovery and isolation of microbial natural product GENOME MINERS Robert J. Deeth (from left),
tifying culture conditions in Sylvie Lautru, and Challis are part of the team that researchers have predicted which the product could be pro- used genetic information to find a new natural product. and then discovered a pre- duced by the organism and isoviously unknown natural product. lated. Surprisingly, even though Brian O.BachThe process of discovering the gene cluster encodes a nonri- mann, an assisnatural products from microbes bosomal peptide synthetase con- tant professor of is usually long and laborious. taining only three modules, which chemistry at VanH9N Genome mining—that is, search- usually means that the product derbilt Universiing agenome for DNAsequences would be a tripeptide, coelichelin ty, says this work that encode enzymes involved in is in fact a tetrapeptide with one "takes a chunk the biosynthesis of particular of the predicted amino acids in- out of the luck products—could provide a sig- corporated twice. component of nificant shortcut, as demonstrat"The fact that it is a tetrapep- natural products Coelichelin ed by Gregory L. Challis and tide rather than a tripeptide is discovery, which coworkers in the chemistry de- very important because it has po- traditionally repartment at the University of tentially far-reaching implications lies on screening a large number Warwick, Coventry, England. for nonribosomal peptide syn- of extracts. The work shows that They have used genome mining thetase multienzymes, which are a little foreknowledge goes a long to identify a previously unknown involved in the biosynthesis of way With a good idea of the natnatural product from the soil- many important microbial natu- ural product structures that a givdwelling bacterium Streptomyces ral products," Challis says. These en biological source may contain, coelicolor. findings suggest that these sys- the task of isolating them and In 2000, Challis' group iden- tems don't always work the way solving their final structure is gready simplified."—CELIA HENRY tified a gene cluster that encodes people assume they do. a new nonribosomal peptide synthetase, which is a modular pro- I N D U S T R I A L S A F E T Y tein system that synthesizes peptides without ribosomes. They predicted that the cluster produces an unknown iron-chelating he Synthetic Organic Chemical Manufacturers Association has launched a mandatory environpeptide, which they called coelment, health, and safety (EHS) and security performance improvement program for its member ichelin. Now, they've actually companies. SOCMA will no longer require its members to pursue qualification under the chemfound the peptide and confirmed ical industry's Responsible Care initiative, run in the U.S. by the American Chemistry Council (ACC). its structure (Nat. Chem. Biol., pub- SOCMA's ChemStewards program, featuring progressive tiers of compliance and third-party verilished online Sept. 11, dx.doi.org/ fication, is better suited than Responsible Care to the needs of the batch manufacturers, distributors, 10.1038/nchembio731). and small producers that make up much of SOCMA's membership, President Joseph G. Acker told "In our approach, we use analy- reporters at a SOCMA conference in Philadelphia last week. The new program was developed in resis of DNA sequence data to pre- sponse to a membership survey, he added. dict structural elements of new Acker said SOCMA will not renew its Responsible Care license with ACC when the current twonatural products and then use this year agreement between the associations expires this month. SOCMA has licensed the program for information to design strategies 15 years, with a deadline of 2008 for membership compliance. for rapidly identifying, purifying, ACC President Jack N. Gerard issued a statement expressing regret that SOCMA is breaking and structurally characterizing ranks on EHS and security. Terry F. Yosie, ACC's vice president for Responsible Care, told C&EN that the compounds," Challis says. SOCMA's decision comes as a surprise, given the group's involvement with ACC in the recent conThey predicted how many and version of Responsible Care to a management systems verification format. which amino acids the product According to Acker, ACC planned to begin charging SOCMA to license the Responsible Care would contain. The information program in October, but he said the prospect of a licensing fee was not a factor in SOCMA's turned out to be crucial for iden- decision.-RICK MULLIN
U
SING GENOME MINING,
SOCMA Opts Out Of Responsible Care
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19, 2005
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