Pitt chemical biologist finds new halogenation enzyme

Discovery is expected to impact pharmaceutical and agricultural industries

2014-09-15

(Press-News.org) PITTSBURGH—Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents in many bioactive compounds has a profound influence on their molecular properties.

One of the Holy Grails in chemical science has been to find the late-stage, site-specific incorporation of a halogen atom into a complex natural product by replacing an sp³ C-H bond (one of the most inert chemical bonds known in an organic compound) with a C-X bond (X=halogen). Until work was undertaken in the laboratory of Xinyu Liu at the University of Pittsburgh, there was no reliable synthetic or biological method known to be able to achieve this type of transformation.

In an article published online on Sept. 14 in Nature Chemical Biology, the group, led by Liu, an assistant professor of chemistry within Pitt's Kenneth P. Dietrich School of Arts and Sciences, has discovered the first enzyme that can accomplish this feat.

Liu and postdoctoral fellow Matthew Hillwig studied bacteria and demonstrated that the WelO5 protein is the first enzyme identified to have the capacity to mediate the regio- and stereospecific replacement of an aliphatic C-H bond to C-Cl bond on a freestanding small molecule. Specifically, they determined this by studying the biogenesis of hapalindole-type alkaloid welwitindolinones in stigonematalean cyanobacteria.

Their work also provides conclusive evidence on a longstanding question regarding the enzymatic origin of chlorine substitution in the biogenesis of hapalindole-type alkaloids in accordance with a proposal that was recently formulated by the Liu group.

It is expected that this discovery will present unprecedented opportunities to evolve new catalysts for selective late-stage halogenations on unactivated carbons in complex molecular scaffolds.

This development could find broad applications in pharmaceutical and agricultural industries, enabling medicinal chemists to tailor synthetic molecules with halogen substituents in order to improve their pharmacological profiles.

INFORMATION: END

ELSE PRESS RELEASES FROM THIS DATE:

Satellite sees Tropical Depression 16-E remnants scooped by Hurricane Odile

2014-09-15

At 11 p.m. EDT on Sunday, September 14, Tropical Depression 16-E was officially a remnant low pressure area. NOAA's GOES-West satellite showed the clouds associated with the remnants being drawn into the massive circulation of nearby Hurricane Odile. At 5 a.m. on Sunday, September 14, Tropical Depression 16-E (TD 16-E) was still holding together despite being close to the circulation of Hurricane Odile. At that time, the center of tropical depression 16-E was located near latitude 14.9 north and longitude 115.3 west. That's about 655 miles (1,055 km) south-southwest ...

Satellites show Edouard's transition into an Atlantic Hurricane

2014-09-15

VIDEO: This GOES-East satellite image animation of Edouard from Sept. 13 through 15 showed the storm consolidating. The eye of the hurricane became visible on and off during Sept. 14 in... Click here for more information. NASA's Terra satellite passed over Tropical Storm Edouard each day from September 12 through 14 and captured imagery of the storm as it grew into a hurricane. NOAA's GOES-East satellite covers the Atlantic Ocean and takes visible images during the day and infrared ...

NASA sees Typhoon Kalmaegi as a whirlpool of clouds in the South China Sea

2014-09-15

NASA's Aqua satellite observed Typhoon Kalmaegi crossing the South China Sea and a satellite image from the MODIS instrument aboard made it look like a whirlpool of clouds. On Sunday, September 14, Kalmaegi passed over northern Luzon, Philippines and emerged into the South China Sea. Typhoon Kalmaegi's maximum sustained winds were near 65 knots (75 mph) making it a category one hurricane on the Saffir-Simpson scale as it moved over the Philippines. On September 15 at 05:15 UTC (1:15 a.m. EDT) the Moderate Resolution Imaging Spectroradiometer aboard NASA's Aqua satellite ...

Number-crunching could lead to unethical choices, says new study

2014-09-15

Toronto – Calculating the pros and cons of a potential decision is a way of decision-making. But repeated engagement with numbers-focused calculations, especially those involving money, can have unintended negative consequences, including social and moral transgressions, says new study co-authored by a professor at the University of Toronto's Rotman School of Management. Based on several experiments, researchers concluded that people in a "calculative mindset" as a result of number-crunching are more likely to analyze non-numerical problems mathematically and not take ...

Researchers develop improved means of detecting mismatched DNA

2014-09-15

Researchers at Johns Hopkins have identified a highly sensitive means of analyzing very tiny amounts of DNA. The discovery, they say, could increase the ability of forensic scientists to match genetic material in some criminal investigations. It could also prevent the need for a painful, invasive test given to transplant patients at risk of rejecting their donor organs and replace it with a blood test that reveals traces of donor DNA. In a report in the September issue of The Journal of Molecular Diagnostics, the research team says laboratory tests already show that ...

Freshman girls know how to eat healthy but lack confidence in their ability to do it

2014-09-15

URBANA, Ill. – Female college freshmen understand the benefits of eating healthy foods and know which foods they should include in their diets. But they lack confidence in their ability to act on that knowledge, especially when it comes to getting enough calcium, says a new University of Illinois study. "The women in our study weren't very confident about their ability to eat a healthful diet, especially if they had to do something physical like chop vegetables or go shopping. The motivation just wasn't strong if they were at a party or in places where there were other ...

Study: Web-based training can reduce campus rape

2014-09-15

Web-based training targeted at college-aged men is an effective tool for reducing the number of sexual assaults on U.S. campuses, according to a researcher in the School of Public Health at Georgia State University. The RealConsent program reduced sexually violent behavior and increased the likelihood a male student would intervene to prevent a sexual assault, said Dr. Laura Salazar, associate professor of health promotion and behavior, who published the findings in the paper, "A Web-Based Sexual Violence Bystander Intervention for Male College Students: Randomized Controlled ...

Study indicates hunting restrictions for tapirs may not be enough

2014-09-15

A published study indicates that lowland tapir populations may continue to drop in French Guiana, despite recent restrictions on hunting. Researchers from the Office National de la Chasse et de la Faune Sauvage in French Guiana and San Diego Zoo Global reviewed data retrieved from camera traps in the Nouragues National Reserve over the last four years and compared this data to current harvest rates in the region. "In 2011, restrictions were placed on hunting tapirs in French Guiana," said Matthias Tobler, a scientist with the San Diego Zoo Institute for Conservation Research. ...

Northeastern University Researchers Develop Novel Method for Working with Nanotubes

2014-09-15

An interdisciplinary team of researchers led by Northeastern University has developed a novel method for controllably constructing precise inter-nanotube junctions and a variety of nanocarbon structures in carbon nanotube arrays. The method is facile and easily scalable, which will allow the researchers to tailor the physical properties of nanotube networks for use in applications ranging from electronic devices to CNT-reinforced composite materials found in everything from cars to sports equipment. Their findings were published in the journal Nature Communications in ...

iPhone Chemistry: Elements of a smartphone

2014-09-15

WASHINGTON, Sept. 15, 2014 — By now, we've got all the details about Apple's latest iPhone, and the lines are probably forming somewhere for the Sept. 19 launch. But what do you really know about the guts of the iPhone 6, or any smartphone for that matter? Reactions teamed up once again with the Compound Interest blog to reveal the chemical elements found inside your smartphone. Learn all about it at http://youtu.be/66SGcBAs04w. INFORMATION: Subscribe to the series at Reactions YouTube, and follow us on Twitter @ACSreactions to be the first to see our latest videos. ...

LAST 30 PRESS RELEASES:

Global cervical cancer vaccine roll-out shows it to be very effective in reducing cervical cancer and other HPV-related disease, but huge variations between countries in coverage

Personalised “cocktails” of antibiotics, probiotics and prebiotics hold great promise in treating a common form of irritable bowel syndrome, pilot study finds