Science Concentrates SYNTHETIC BIOLOGY
Researchers design smallest genome yet Minimal bacterial genome contains 473 genes, 149 of which still have unknown functions Researchers are a step closer to figuring out the minimum number of genes required to sustain life. Clyde A. Hutchison III and J. Craig Venter of the J. Craig Venter Institute, in La Jolla, Calif., and coworkers have designed and synthesized the smallest bacterial genome yet known (Science 2016, DOI: 10.1126/science.aad6253). The researchers started with a genome they’d first synthesized in 2010, which contained 900 genes from the bacterium Mycoplasma mycoides (C&EN, May 24, 2010, page 10). They then used information from the biochemical literature to identify genes they could remove and still sustain bacterial life, forming a hypothetical “minimal genome.” But a genome produced from that design was a failure: When inserted into a recipient cell, it couldn’t sustain life. After adding genes back in three more
rounds of design and testing, the researchers ended up with a genome containing 473 genes that could form viable bacteria. They were surprised by how many “quasi-essential” genes they retained in the designer genome. Those genes weren’t necessary to keep the cell alive, but they were necessary for robust cell growth. Christopher Voigt, an expert on synthetic biology at Massachusetts Institute of Technology, doesn’t know whether those genes needed for growth are significant. “It’s an open question whether an organism with a human-designed simplified genome can achieve the same growth as a natural one,” he says. “Is the inherent complexity a necessity, or is it disposable?” Surprisingly, the researchers still don’t know the function of 149 genes in their
The reduced genome (red circle) has about half the DNA base pairs of the starting genome (blue). The red bars inside the blue circle represent retained genome regions. The white numbers indicate genome segments. designer genome. And that’s why robust growth wins out over an absolute minimum genome. “We’re interested in an organism with a workable growth rate so we can determine the functions of the remaining genes,” Hutchison says.—CELIA
ARNAUD
Z-Alkenyl halides made easy Tough-to-prepare motif succumbs to metathesis One of organic chemists’ dirty little secrets, chlorides, and fluorides (Nature 2016, says Boston College’s Amir Hoveyda, is how DOI: 10.1038/nature17396). Cross-metathhard it is to make alkenyl halides, a motif that esis reactions are those that use a metal catfeatures a halide attached to a double bond. alyst to get the carbons in two carbon-car“We use them all the time for cross-coubon double bonds to swap their bonding pling,” he says, “but we never talk about how partners and form two new carbon-carbon we make them.” The truth, Hoveyda says, is double bonds. This reaction exchanges the that making alkenyl bromides and chlorides substituents attached to the carbon atoms. is difficult, and making alkenyl fluorides is A molybdenum catalyst developed by almost unheard of—unHoveyda’s group makes N til now. this cross-metathesis N Hoveyda, along with O O reaction work well with Boston College chemists Z-dihaloalkenes, which N Cl Ming Joo Koh, Thach came as a surprise to F T. Nguyen, and Hanmo Hoveyda, he says, after S Zhang and MIT’s Richstructural analysis ard R. Schrock, has now Hoveyda’s group used crosssuggested the reaction used cross-metathesis metathesis to make the Z-alkenyl wouldn’t work. “Our chemistry to prepare fluoride in this derivative of the only hope was that Z-alkenyl bromides, antidepressant perphenazine. the reaction interme-
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C&EN | CEN.ACS.ORG | MARCH 28, 2016
diates, although they are not very stable, would stick around long enough to do the chemistry, and lo and behold they did,” he says. The reaction works efficiently to give Z-alkenyl halides—also known as cis-alkenyl halides—in high yield. It also tolerates a variety of functional groups, suggesting the transformation could be used in the late stages of a synthetic scheme. “Hoveyda and colleagues’ transformation offers a powerful strategy for preparing cis-alkenyl halides, especially given that alkenes are abundant motifs in fine chemicals such as pharmaceuticals and agrochemicals,” writes David Sarlah, a chemistry professor at the University of Illinois, Urbana-Champaign, in a commentary on the new work. Hoveyda tells C&EN that an air-stable paraffin capsule containing the catalyst will be commercially available from Aspira Scientific in the near future.—BETHANY
HALFORD
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