Patent review – biocatalysts

David Hughes at Cidara Therapeutics reported in ORPD on a patent literature search pertaining the use of biocatalysts to effect chemical transformations. He covers some P450 mediated cyclopropanation, reductive amination, Diels-Alder (artificial enzyme), nitrilase (conversion of nitrile to carboxylic acid)  reactions all catalyzed by enzymes.

 

ORPD paper

Nuphar alkaloid chemical biology

Jimmy Wu and co-workers reported in ACIE on the formal synthesis of nuphar alkaloids and their apoptotic activity. Did you know that the second “p” in “apoptosis” is silent and it is pronounced “apa-tosis”? The Greek word “apoptosis” means “falling off” or “dropping off” of flower petals or tree leaves.

 

ACIE paper

LmbF is a PLP-enzyme

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.

Chemical Science paper

Marmycin A synthesis

Raphael Rodriguez and co-workers at CNRS UMR have reported in Nature Chemistry on the synthesis of marmycin A.

Nature Chemistry 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

Asperchalasine A

Here’s a natural product isolation paper that was published in ACIE. Yonghui Zhang and co-workers report on the isolation of asperchalasine A, which induced G-1 phase cell cycle arrest by reducing the expression of cyclin A, CDK2, and CDK6 in cancer cells but not in normal cells at 20 micromolar (pretty high concentration so not so potent in my opinion).

ACIE paper

Cyclopropenones – a chemical biology tool

Jennifer Prescher and colleague at UC Irvine have reported in JACS on the potential for using cyclopropenones to conjugate proteins.

JACS paper

Molecular prosthetics

Martin Burke’s group is making use of their small molecules that they’re synthesizing.

JACS paper

Nannocystin A

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).

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.

Staphyloferrin B synthesis

Elizabeth Nolan and co-workers from MIT have reported in JACS on the synthesis of staphyloferrin B, an iron chelating natural product found in bacteria.

JACS paper