Naturalproductman’s Blog

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Archive for the ‘Biosynthesis’ Category

From a trans to cis olefin and oxidations

Posted by naturalproductman on April 14, 2016

Kenji Watanabe and co-workers from the University of Shizuoka have reported in ACIE on an enzyme system (PsoE (glutathione S-transferase) and PsoF (flavin-containing monooxygenase)) that involves glutathione conjugation of a polyolefinic natural product (presynerazol) to form a glutathione adduct intermediate, which in turn is oxidized to the sulfoxide (by flavin hydroperoxide) and eliminates to form a cis-olefin (synerazol).

 

ACIE paper

Posted in Biosynthesis, Polyketides | Leave a Comment »

Roseoflavin biosynthesis

Posted by naturalproductman on April 11, 2016

Matthias Mack and co-workers from Mannheim University have reported in ACIE on the identification of an enzyme found in the biosynthesis of roseoflavin.

 

ACIE paper

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

Mannolides A-C

Posted by naturalproductman on April 7, 2016

Jian-Min Yue and co-workers from the Chinese Academy of Sciences have reported in Organic Letters on the isolation of mannolides A-C.

OL paper

Posted in Biosynthesis, Cancer, Diterpenoids | Leave a Comment »

Precolibactin synthesis/structural revision

Posted by naturalproductman on March 31, 2016

Seth Herzon and co-workers from Yale have reported in JACS on the synthesis of precolibactin. It’s another example of why total synthesis is important. But another interesting aspect about this natural product is that previous efforts used bioinformatics approaches to propose the thiazoline-thiazole chain – when in fact the natural product has a terminal cysteine appended where this thiazoline-thiazole chain was proposed to exist.

 

JACS paper

Posted in Biosynthesis, Peptides, Structural Reassignment, Total Synthesis | Leave a Comment »

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 »

 
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