Tryptophan labeling

Michael Taylor and co-workers from the University of Wyoming reported in JACS on a method to label tryptophan residues using an N-carbamoyl pyridinium salt and light.

JACS paper

Mechanism of a Diels-Alderase Enzyme

Paul Race and co-workers from the University of Bristol have reported in JACS on the details of how an enzyme catalyzes a Diels-Alder reaction using crystal structures and enzyme assays. The enzyme is called spirotetronate cyclase AbyU and is key in forming the macrocyclic structure of abyssomicin C.

 

JACS paper

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

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

FtmOx1 forms the endoperoxide in verruculogen

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

Going from a diol to a tetrahydropyran in salinomycin

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

Enzyme from bacteria breaks down nicotine

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

Welcome to the future

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

Cyclopropanation with iron(III) phthalocyanine

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

MAP4K4 for neurodegenerative diseases

Herbert Waldmann and co-workers at Technische Universität Dortmund have reported in ACIE on MAP4K4 as a target for neurodegenerative diseases.

ACIE paper

Eudistidine A

The NCI does some nice work with natural products. Kirk Gustafson and co-workers at Bethesda have reported in JACS on some new natural products that block the interaction between p300 and HIF1alpha.

JACS paper