December 22, 2003
Volume 81, Number 51
CENEAR 81 51 pp. 39-50

ISSN 0009-2347



Sometimes, chemists just won't let well enough alone--especially when they think they can improve on nature. For example, Homme W. Hellinga and colleagues at Duke University used computational chemistry to redesign proteins to perform new nonnatural functions [Nature, 423, 185 (2003)]. When the proteins were synthesized, they indeed worked as planned.

CLOSE MATCH Baker and coworkers found that the crystal structure (red) of a synthesized protein with a new "fold" was a remarkably good match with the computationally designed model (blue) on which it was based. © SCIENCE

David Baker of the University of Washington, Seattle, and coworkers conceived a large protein with a previously unknown shape, designed it computationally, synthesized it, determined its structure, and found it to be an extremely close match with the original conception [Science, 302, 1364 (2003)].

The first microorganisms that produce a nonnatural amino acid and incorporate it into proteins were created by Peter G. Schultz of Scripps and coworkers [J. Am. Chem. Soc., 125, 935 (2003)]. The modified bacteria synthesize proteins using a 21st amino acid, p-aminophenylalanine, in addition to the 20 that are common to all other life forms. And the first method for adding nonnatural amino acids to the genetic code of a eukaryotic organism (yeast) was devised by the same group and demonstrated by expressing proteins with 21 amino acids each, instead of the usual 20 [Science, 301, 964 (2003)]. "We have effectively removed a billion-year constraint on our ability to manipulate the structure and function of proteins," Schultz said.

After long-standing efforts by several groups, Tillman U. Gerngross of Dartmouth College and coworkers there and at GlycoFi Inc., Lebanon, N.H., genetically engineered yeast to produce proteins with glycosylation patterns similar to those in human proteins [Science, 301, 1244 (2003)]. The technique could lead to the production of novel therapeutics.

In work with potential implications for DNA sensing and genetic tissue typing, Eric T. Kool and coworkers at Stanford University created an alternative genetic system based on DNA bases of expanded size [Science, 302, 868 (2003)].

In the area of tissue engineering, the use of biodegradable polymer scaffolds to grow 3-D tissues from embryonic stem cells was demonstrated by Robert S. Langer of MIT and coworkers [Proc. Natl. Acad. Sci. USA, 100, 12741 (2003)].

A collaborative French team sponsored by Aventis produced hydrocortisone biosynthetically in recombinant yeast from simple carbon compounds. Hydrocortisone, an anti-inflammatory steroid and key synthetic intermediate, has been made industrially using multistep chemistry and microbial bioconversion [Nat. Biotechnol., 21, 143 (2003)].

Another French group--Bilal Camara of Université Louis Pasteur, Strasbourg, and coworkers--discovered the mechanism of biosynthesis of the commercially important plant pigment bixin and planned to use the pathway to make bixin-producing tomatoes [Science, 300, 2089 (2003)].


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