SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis

Pericyclic reactions—which proceed in a concerted fashion through a cyclic transition state—are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon–carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels–Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-l-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels–Alder and hetero-Diels–Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme ‘toolboxes’. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

Nature doi: 10.1038/nature23882

England’s National Health Service in trouble, services may soon be CLOSED to new patients

(Natural News) Surgery and dental services in England may soon be unavailable to new patients, according to reports by the Daily Mail. Majority of England’s general practitioners (GPs) want to close their surgery lists to new patients in protest at the strain on the National Health Services (NHS), according to survey results reported in the...

Viking Warrior In Famous Grave Was A Woman

This one goes out to all my fellow shieldmaidens: researchers have confirmed through ancient DNA testing that the warrior buried in a famous Viking grave was a woman. Researchers have excavated hundreds of Viking-era graves at Birka, a UNESCO World Heritage Site in Sweden. One of the graves, originally excavated in the 1880s, was particularly noteworthy for both its position — on a prominent terrace adjacent to what had been a garrison — and for its grave goods, which included a varie

New Publication Considers Past and Future of U.S.-Iran Science Engagement

For over 15 years, the National Academies of Sciences, Engineering, and Medicine have organized workshops and other cooperative activities between U.S. and Iranian scientists on topics ranging from earthquake preparedness to urban air pollution to wetland conservation. More than 1,500 scientists, engineers, and medical professionals from about 120 institutions in both countries have participated in these activities, which are intended to contribute to global science in areas of mutual interest. U.S.-Iran Engagement in Science, Engineering, and Health: A Resilient Program, But an Uncertain Future, a new publication authored by Glenn Schweitzer, director of the National Academies' Program for Central Europe and Eurasia, documents the history and details of the Academies' program of science engagement with Iran from 2010 to 2016. The publication also identifies lessons learned from past cooperative activities – for example, the importance of involving both highly respected leaders in the field of interest and early career professionals who can sustain joint efforts for years and even decades. The publication also offers a perspective on future science engagement with Iran.

Electric avenue

Where to with electric vehicles? Christchurch is introducing a fleet of electric cars, for business and public use. That’s adding about 100 new electric vehicles (“EV”) cars to the existing 3,000 in NZ. That’s less than 0.1% of the over 3.5 million light vehicles registered here.   The more significant point with the Christchurch cars, though, […] The post Electric avenue appeared first on Sciblogs.

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