GLYCOPROTEINS MADE TO ORDER CHEMICAL BIOLOGY: First homogeneous, eukaryote-type N-glycoproteins from prokaryotes
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N INTERNATIONAL TEAM has for the first
time prepared homogeneous N-glycoproteins of the type produced by eukaryotic organisms, including humans, from prokaryotes. In those protein molecules, branched sugars of uniform composition are linked to specific arginines. The work could lead to monoclonal antibody medications with improved potencies and fewer side effects and could ease studies on the biological effects of different protein glycosylation patterns, which play important functions that remain incompletely understood. Several groups have been trying to produce N-glycoproteins (N-glycans) in bacteria, which typically do not glycosylate their proteins. Microbiologist Markus Aebi of the Swiss Federal Institute of Technology, Zurich, and coworkers previously engineered Escherichia coli with genes from Campylobacter jejuni, a gastroenteritiscausing bacterium that is unusual in being able to glycosylate its proteins. But the engineered E. coli made glycoproteins with an immunogenic C. jejuni glycan and an unusual and unwanted bacillosamine sugar linked to the protein. Now, Aebi, protein glycosylation specialist Lai-Xi Wang of the University of Maryland School of Medicine, and coworkers report for the first time that E. coli can be engineered with C. jejuni genes to make bacillosamine-free N-glycoproteins that can be elaborated enzymatically into nonimmunogenic eukaryote-type N-glycoproteins with customized glycans (Nat. Chem. Biol., DOI: 10.1038/nchembio.314). They did this by pro-
ducing N-glycoproteins in C. jejuni-engineered E. coli cells, purifying them, and then swapping their glycans for eukaryotic ones. Homogeneous N-glycoproteins can also be made in other ways, such as by chemical synthesis or by expression in engineered yeast. But chemical synthesis is extremely challenging and time-consuming. And Aebi and Wang believe the bacterial approach will be ENGINEERING N-GLYCOSYLATION faster, less laborious, and In the new technique, metabolically altered higher yielding than creatE. coli produce a lipid-linked hexasacchaing them in yeast, which are ride. Two engineered-in C. jejuni enzymes eukaryotes. (pink and light green) attach it to a protein For instance, yeast has (blue) in the periplasm (between the cytoto be engineered differplasmic and cell membranes). In vitro, the ently for each different glycans are trimmed and a tailored glycan type of glycan (glycoform), is added enzymatically. whereas the new method “will have the flexibility to produce a series of homogeneous glycoforms using one type of engineered E. coli,” Wang says. “Moreover, it can also produce unnatural glycoforms that the yeast system wouldn’t be able to produce.” The yeast approach is controlled by Merck & Co. as a result of its 2006 acquisition of the biotech company GlycoFi, which developed it. Bacterial N-glycosylation specialist Christine M. Szymanski of the University of Alberta, in Edmonton, says the new study represents “the first time anyone has been able to use a bacterial system to synthesize a homogeneous eukaryotic N-linked glycoprotein. There are other systems that have been used to do this, but they all come with their own problems. This one shows much promise but requires further development to make the system commercially feasible.”—STU BORMAN
MERGERS AND ACQUISITIONS Dow will exit styrenics with sale to Bain Capital Dow Chemical has agreed to sell its Styron division to the private equity firm Bain Capital for $1.6 billion. Dow formed Styron last summer as a means of carving out polymer businesses that no longer fit its specialty chemical strategy. Styron generated $3.5 billion in revenues last year. The business includes styrene derivatives such as acrylonitrile-butadiene-styrene and expandable polystyrene. It also houses Dow’s polycarbonate, latex, and synthetic rubber operations, as well as production of some specialty polymers.
Dow’s 50% stake in Americas Styrenics, a polystyrene joint venture with Chevron Phillips Chemical, is included as well. “We are committed to further focusing our portfolio by shedding nonstrategic assets that can no longer compete for growth resources inside the company,” says Dow CEO Andrew N. Liveris. Dow has sold a number of businesses since its acquisition of Rohm and Haas last April, including Rohm and Haas’s powder coatings and Morton Salt units as well as its own calcium chloride and acrylic monomers and polymers businesses. Ad-
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ditionally, Dow is in talks to form a joint venture for its polyethylene businesses. This isn’t Bain’s first foray into chemicals. Earlier it acquired Rhodia’s phosphate business and took it public, purchased coatings maker SigmaKalon and sold it to PPG Industries, and took over the German chemical distributor Brenntag before selling it to another private equity firm. Paul Mann, a chemical stock analyst with Morgan Stanley, says the price Bain is paying for Styron exceeds his expectation of up to $1.2 billion.—ALEX TULLO
ADAPTED FROM NAT. C H E M. BIOL.
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