n e w s of t h e w e e k that the organism could not go beyond the first steps in making erythronolide B, an erythromycin precursor. Specifically, it could not put two propionate molecules By engineering a strain of bacteria to ac- together to make a diketide intermediate cept synthetic organic intermediates, a called P-hydroxy-a-methylvalerate. team of U.S. researchers has created anaThat strategy allows the investigators to logs of the antibiotic erythromycin [Sci- then add synthetic diketides with structurence, 277,367 (1997)]. The achievement al variations to the culture as substitute incould lead to a general approach to the termediates. For example, the organism synthesis of antibiotics that lack the made erythronolide B with its usual ethyl stomach-irritating side effects of erythro- group when they added the normal intermycin, that overcome bacterial resis- mediate, hydroxymethylvalerate. When they introduced an intermedi——— ate with a longer alkyl group, the bacteria incorporated it into Diketide substitutes yield a polyketide with a butyl group erythromycin analogs attached. And yet another substitute diketide gave a polyketide with a hanging benzyl group. These synthetic polyketides can be processed stillfiirtherto yield erythromycin analogs. In the last steps of commercial production of erythromycin by R = CH 3 , CH2CH2CH3, or C 6 H 5 fermentation with SaccharoR' = /Y-acetylcysteamine polyspora erythrea, other enzymes put a hydroxyl group Note: When R = CH 3 , analog is 6-deoxyerythronolide B. and two sugar molecules onto erythronolide B to form erythrotance to erythromycin itself, and that are mycin. The researchers find that incubating their benzylated and w-butylated more resistant to low pH. The researchers induced the biosyn- polyketides with S. erythrea gives nicely thetic machinery of Streptomyces (a mold- hydroxylated, glycosylated erythromycin like bacteria) to make nonnatural poly- analogs with antibacterial activity. ketides—structurally complex molecules Stephen Stinson that form the core of many antibiotics. The collaborators include chemical engineering professor Chaitan Khosla and postdoctoral fellow John R. Jacobsen at Stanford University; C. Richard Hutchinson, professor of medicinal chemistry and bacteriology at the University of Wiscon- An analysis by the Clinton Administration sin, Madison; and biochemistry professor of thefirstthree years of the North AmerDavid E. Cane at Brown University. ican Free Trade Agreement (NAFTA) indi"It's very important, very significant cates that the controversial treaty has acwork," says Leonard Katz, who works in complished everything it set out to do. Acinfectious disease discovery research at cording to the report, exports and imports Abbott Laboratories, Abbott Park, 111. are both up, employment is up, and enviKatz himself is a pioneer in tracing the ronmental problems are decreasing. modular enzymes that mediate the multiData on changes in chemical trade step biosynthesis of polyketides such as show modest increases in trade between erythromycin. the U.S. and Mexico and vice versa. Be"It's a continuation of work they start- tween 1993 and 1996, U.S. chemical exed before," Katz continues. "Now they're ports to Mexico rose from $3.4 billion to making a complete polyketide in one $5.1 billion. This 50% increase compares host, then inserting it into another host favorably with the 37% increase in the to make the whole erythromycin analog. value of U.S. chemical exports to nonNow one can think about making com- NAFTA countries. Mexican tariffs on U.S. pounds that are true erythromycin ana- chemicals and allied products dropped from 10% to 4%, on average, and tariffs logs, not just polyketides." The team altered the enzyme system so were eliminated completely on 31% of
Engineered bacteria make novel antibiotics
NAFTA report paints rosy scenario
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HJLY21. 1997C&EN
m> the imported chemical products previously subject to duty. U.S. chemical imports from Mexico more than doubled during the same period, rising from $600 million to $1.4 billion. However, the report indicates that NAFTA played no role in this increase, since U.S. tariffs imposed on imports of Mexican chemicals and allied products were only about 1% even prior to 1993. As the report points out, prior to NAFTA's implementation the Mexican government exercised a virtual monopoly over production, sale, and pricing of petrochemicals in Mexico. NAFTA required Mexico to open petrochemical production and sales to U.S.firms,a change that has allowed U.S. producers to sell high-value-added petrochemical products to Mexican end users for thefirsttime. Perhaps that's the reason U.S. direct investment in chemical manufacturing in Mexico declined 47%from1993 to 1995 even as U.S. companies continued to invest heavily both in the U.S. and abroad. But economics and trade are only part of what NAFTA is about. Serious concerns about the agreement's effects on the U.S. workforce and the environment have surrounded NAFTA. These concerns have not eased. For example, AFLCIO President John J. Sweeney still contends that "NAFTA rewards and encourages companies that abandon their U.S. production facilities in order to take advantage of low wages and lax enforcement of labor and environmental standards in Mexico." David Hanson
Initial actions bode well for '98 R&D funding The fiscal 1998 federal funding bills have begun winding their way toward enactment. The House Appropriations Committee is the place where that annual journey begins. So far, the committee has been fairly generous in doling out science funding, particularly considering that many programs are being cut to bring federal spending into balance with federal revenues by 2002. Here's a quick, initial look at what's up and what's down infiscal1998, based on the committee's work. At the National Science Foundation, funding for research and related activities—the account that funds academic researchers—would rise 4.3%, or $106 million, to $2.5 billion. That is $23 million
