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Archive for the ‘Biosynthesis’ Category

Biosynthetic origin of L-allo-isoleucine in desotamides and marformycins

Posted by naturalproductman on January 18, 2016

Jianhua Ju and co-workers at the Chinese Academy of Sciences have reported in JACS on the biosynthetic origin of L-allo-isoleucine. The culprit is a PLP-enzyme.

 

JACS paper

Posted in Biosynthesis, Enzymatic, Enzymes, Peptides | Leave a Comment »

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 »

LmbF is a PLP-enzyme

Posted by naturalproductman on October 21, 2015

Jiri Janata and co-workers from ASCR in the Czech Republic have reported in Chemical Science on the identification of the enzyme, LmbF, in the biosynthesis of lincomycin.

lincomycin

Chemical Science paper

Posted in Alkaloids, Biosynthesis, Chemical Biology, Tetrahydropyrans | Leave a Comment »

From gene clusters to biosynthesis of natural products

Posted by naturalproductman on October 16, 2015

Leadlay (University of Cambridge) and Sun (Wuhan University) and co-workers have reported in Chemical Science on thiotetronate biosynthesis.

gene

Chemical Science paper

Posted in Biosynthesis, Mechanistic, Thiotetronate | Leave a Comment »

[6+4] vs [4+2]

Posted by naturalproductman on October 16, 2015

Kendall Houk and co-workers have reported in JACS on a biosynthetic study of heronamide A using DFT calculations to study the [6+4] cycloaddition.

6+4

JACS paper

Posted in Biosynthesis, Cycloaddition, DFT | Leave a Comment »

Epicolactone synthesis

Posted by naturalproductman on October 13, 2015

Dirk Trauner and co-workers reported in Nature Chemistry on a biomimetic synthesis of epicolactone.

epicolactone

Nature Chemistry paper

Posted in Biosynthesis, Cascade Reactions, Total Synthesis | 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.

salinomycin

ACIE paper

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

Nannocystin A

Posted by naturalproductman on July 17, 2015

Dominic Hoepfner and co-workers from Novartis have reported in ACIE on nannocystin A, which had similar binding properties with didemin B on EF-1alpha (elongation factor 1 inhibitor).

nannocystin A

ACIE paper

Mark Brönstrup and co-workers at Helmholtz Zentrum für Infektionsforschung also reported on the isolation of this small molecule. I wonder if there’s a relationship between the two studies.

ACIE paper

the novartis paper states that their study parallels the work in helmholtz. I guess the two studies just coincidentally resulted in the isolation of the same compound.

Posted in Biosynthesis, Cancer, Chemical Biology, Macrocycles, Macrolides, Peptides | Leave a Comment »

Alzmaphorazine B synthesis

Posted by naturalproductman on June 6, 2015

Christopher Vanderwal and colleague have reported in JACS on a synthesis of alzmaphorazine B.

alkaloid

JACS paper

Posted in Alkaloids, Biosynthesis, Total Synthesis | 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.

alkaloid

ACIE paper

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

 
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