Naturalproductman’s Blog

Hey, is that a natural product?!

Archive for the ‘Enzymes’ Category

FtmOx1 forms the endoperoxide in verruculogen

Posted by naturalproductman on November 24, 2015

Here’s a great Nature paper from a three lab collaboration (Lixin Zhang lab at Carnegie Mellon University, Pinghua Liu lab at Boston University, and Yan Jessie Zhang lab at UT Austin) that characterized the enzyme that forms the endoperoxide-containing natural product, verruculogen. The enzyme is an alpha-ketoglutarate dependent iron containing enzyme.


What is interesting about this enzyme is that it forms a “Compound I” species (iron oxo complex), which in turn forms a tyrosine radical within the enzyme, and this tyrosine radical is what abstracts the C-H hydrogen in the starting material, fumitremorgin B. The resulting allylic radical comes together with a molecule of oxygen that in turn cyclizes to form an endoperoxide-containing radical intermediate. This radical intermediate abstracts the tyrosine hydrogen atom to reform a tyrosine radical and verruculogen.

The process of the iron-oxo intermediate abstracting a hydrogen atom from tyrosine reminds me of the way cyclooxygenase enzymes (COX1 and COX2 enzymes) work to form the endoperoxide, prostaglandin H2, from arachidonic acid. Furthermore, if you recall Michael Green’s work published in Science last year, there was a cytochrome P450 enzyme that also removes a hydrogen atom from a nearby tyrosine residue to form a tyrosine radical.


Nature paper

Posted in Alkaloids, Biosynthesis, Enzymes | Leave a Comment »

Going from a diol to a tetrahydropyran in salinomycin

Posted by naturalproductman on September 25, 2015

Peter Leadlay and co-workers from the University of Cambridge have reported in ACIE on the enzyme that makes the tetrahydropyran ring in salinomycin. The tetrahydropyran is proposed to come from a diol where one of the hydroxy groups is in the beta-position to a ketone and subsequently dehydrates to form an enone. The enone undergoes an intramolecular Michael reaction to form the tetrahydropyran. However, when the reaction is done in vitro with the purified enzyme, they don’t see the enone intermediate, so I wonder if it is a processive reaction; in other words, the enone forms in the enzyme active site without being released and cyclizes to the tetrahydropyran.


ACIE paper

Posted in Biosynthesis, Chemical Biology, Enzymes, Mechanistic, Polyketides, Tetrahydropyran | Leave a Comment »

Enzyme from bacteria breaks down nicotine

Posted by naturalproductman on August 7, 2015

I’m sure this is not what the authors meant by battling nicotine addiction, but it made me laugh to think that a bacterial enzyme will be responsible to fight nicotine addiction – and immediately I thought that are we going to spray the smokers with this bacteria that has this enzyme?

JACS paper

Posted in Enzymes | Leave a Comment »

Welcome to the future

Posted by naturalproductman on August 7, 2015

I read the title of this paper and immediately thought of David Baker’s work. I guess we are getting closer to having a logical approach available to design our own protein catalysts.
JACS paper

Posted in Computational, Enzymes, Methodology | 2 Comments »

Cyclopropanation with iron(III) phthalocyanine

Posted by naturalproductman on May 2, 2015

Emily Balskus and colleague have reported in ACIE on an iron(III) phthalocyanine catalyst that can perform cyclopropanation reactions. Reminds me of the P450 version that was published a few years back.

ACIE paper

Posted in Enzymes, Iron, Methodology, Transition Metal | Leave a Comment »

Penitrem biosynthesis

Posted by naturalproductman on April 12, 2015

Hideaki Oikawa and co-workers at Hokkaido University have reported in ACIE on the enzymatic biosynthesis of penitrem.


ACIE paper

Posted in Biosynthesis, Cyclobutanes, Diterpene, Enzymes, Indoles | Leave a Comment »

Corvol ethers A and B biosynthesis

Posted by naturalproductman on March 25, 2015

Jeroen Dickschat and co-workers at Technische Universität Braunschweig have reported in ACIE on some terpene biosynthesis by characterizing a sesquiterpene cyclase enzyme.

ACIE paper

Posted in Biosynthesis, Enzymes, Sesquiterpenes | Leave a Comment »

Terpene cyclization involving carbons switching

Posted by naturalproductman on March 5, 2015

Tomohisa Kuzuyama and co-workers at the University of Tokyo have reported in ACIE on an mechanistically interesting terpene cyclization involving two carbons switching.


ACIE paper

Posted in Biosynthesis, Enzymes, Mechanistic, Proteins | Leave a Comment »

Cycloclavine biosynthesis

Posted by naturalproductman on March 5, 2015

Sarah O’Connor and co-workers from the John Innes Centre in the UK have reported in ACIE on the biosynthesis of cycloclavine.


ACIE paper

Posted in Alkaloids, Biosynthesis, Enzymatic, Enzymes, Methodology | Leave a Comment »


Posted by naturalproductman on February 22, 2013

Hayamitsu Adachi and co-workers from BIKAKEN have reported in JNP on a novel VEGF receptor tyrosine kinase inhibitor from bacteria. The only problem I see with this compound – from a toxicologist’s perspective – is that this is a quinone, and thus a very reactive electrophile. If this kind of functional group is used as a drug, who knows what other things it will react with in the body – be it DNA, proteins, etc…

JNP paper

Posted in Alkaloids, Enzymes, Protein Targets, Proteins | Leave a Comment »


Get every new post delivered to your Inbox.

Join 83 other followers