NEWS OF THE WEEK

C H E M I C A L B I O L O G Y

GENOME MINING HITS PAY DIRT DNA sequence guides discovery and isolation of microbial natural product

U SING GENOME MINING, researchers have predicted and then discovered a pre­

viously unknown natural product. The process of discovering

natural products from microbes is usually long and laborious. Genome mining—that is, search­ing agenome for DNAsequences that encode enzymes involved in the biosynthesis of particular products—could provide a sig­nificant shortcut, as demonstrat­ed by Gregory L. Challis and coworkers in the chemistry de­partment at the University of Warwick, Coventry, England. They have used genome mining to identify a previously unknown natural product from the soil-dwelling bacterium Streptomyces coelicolor.

In 2000, Challis' group iden­tified a gene cluster that encodes a new nonribosomal peptide syn­thetase, which is a modular pro­tein system that synthesizes pep­tides without ribosomes. They predicted that the cluster pro­duces an unknown iron-chelating peptide, which they called coel­ichelin. Now, they've actually found the peptide and confirmed its structure (Nat. Chem. Biol., pub­lished online Sept. 11, dx.doi.org/ 10.1038/nchembio731).

"In our approach, we use analy­sis of DNA sequence data to pre­dict structural elements of new natural products and then use this information to design strategies for rapidly identifying, purifying, and structurally characterizing the compounds," Challis says.

They predicted how many and which amino acids the product would contain. The information turned out to be crucial for iden­

tifying culture conditions in which the product could be pro­duced by the organism and iso­lated. Surprisingly, even though the gene cluster encodes a nonri­bosomal peptide synthetase con­taining only three modules, which usually means that the product would be a tripeptide, coelichelin is in fact a tetrapeptide with one of the predicted amino acids in­corporated twice.

"The fact that it is a tetrapep­tide rather than a tripeptide is very important because it has po­tentially far-reaching implications for nonribosomal peptide syn­thetase multienzymes, which are involved in the biosynthesis of many important microbial natu­ral products," Challis says. These findings suggest that these sys­tems don't always work the way people assume they do.

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GENOME MINERS Robert J. Deeth (from left), Sylvie Lautru, and Challis are part of the team that used genetic information to find a new natural product.

Brian O.Bach-mann, an assis­tant professor of chemistry at Van-derbilt Universi­ty, says this work "takes a chunk out of the luck component of natural products discovery, which traditionally re­lies on screening a large number of extracts. The work shows that a little foreknowledge goes a long way With a good idea of the nat­ural product structures that a giv­en biological source may contain, the task of isolating them and solving their final structure is gready simplified."—CELIA HENRY

Coelichelin

I N D U S T R I A L S A F E T Y

SOCMA Opts Out Of Responsible Care

T he Synthetic Organic Chemical Manufacturers Association has launched a mandatory environ­ment, health, and safety (EHS) and security performance improvement program for its member companies. SOCMA will no longer require its members to pursue qualification under the chem­

ical industry's Responsible Care initiative, run in the U.S. by the American Chemistry Council (ACC). SOCMA's ChemStewards program, featuring progressive tiers of compliance and third-party veri­

fication, is better suited than Responsible Care to the needs of the batch manufacturers, distributors, and small producers that make up much of SOCMA's membership, President Joseph G. Acker told reporters at a SOCMA conference in Philadelphia last week. The new program was developed in re­sponse to a membership survey, he added.

Acker said SOCMA will not renew its Responsible Care license with ACC when the current two-year agreement between the associations expires this month. SOCMA has licensed the program for 15 years, with a deadline of 2008 for membership compliance.

ACC President Jack N. Gerard issued a statement expressing regret that SOCMA is breaking ranks on EHS and security. Terry F. Yosie, ACC's vice president for Responsible Care, told C&EN that SOCMA's decision comes as a surprise, given the group's involvement with ACC in the recent con­version of Responsible Care to a management systems verification format.

According to Acker, ACC planned to begin charging SOCMA to license the Responsible Care program in October, but he said the prospect of a licensing fee was not a factor in SOCMA's decision.-RICK MULLIN

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