Search

Chiral heterocyclic compounds are privileged structures in medicinal chemistry. Here, the authors report an in silico strategy for the enzymatic synthesis of pharmaceutically significant chiral N- and O-heterocycles via Baldwin cyclization of hydroxy- and amino-substituted epoxides and oxetanes using epoxide hydrolase mutants.

Connecting conformational dynamics and epistasis has so far been limited to a few proteins and a single fitness trait. Here, the authors provide evidence of positive epistasis on multiple catalytic traits in the evolution and dynamics of engineered cytochrome P450 monooxygenase, offering insights for in silico protein design.

Candida antarctica lipase B (CALB) is a serine lipase. Here, the authors use directed evolution to exchange serine with cysteine in the catalytic triad of the enzyme, thereby obtaining a highly active CALB variant that — unlike the wild type — accommodates bulky substrates.

An intriguing advance in the rational protein engineering of a newly identified glycosyltransferase from Siraitia grosvenorii (UGT74AC2) has been accomplished by Zhoutong Sun, Yuanxia Sun and coworkers for the targeted pharmaceutically significant glucosylation of the polyhydroxy substrate silybin. Using an advanced version of Focused Rational Iterative Site-specific Mutagenesis (FRISM), they were able to evolve mutants that allow the formation of the 3-OH, 7-OH and the 3,7-O-diglycoside products with 94%, > 99% and > 99% regioselectivity, respectively. This can be viewed as a breakthrough because the wildtype UGT74AC2 delivers a difficult to separate mixture of products in a ratio of 22%:39%:39%. Even N- and S-glucosylations were achieved, a likewise unusual accomplishment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The majority of enzymatic Kemp elimination reactions proceed via a well-established acid-base mechanism. Here, the authors show that cytochrome P450 is able to metabolize the leflunomide drug via a redox Kemp elimination, offering new insights into enzyme catalysis.

Arbutin (also called β-arbutin) is a natural product occurring in the leaves of a variety of different plants, the bearberries of the Ericaceae and Saxifragaceae families being prominent examples. It is a β-glucoside derived from hydroquinone (HQ; 1,4-dihydroxybenzene). Arbutin has been identified in traditional Chinese folk medicines as having, inter alia, anti-microbial, anti-oxidant, and anti-inflammatory properties that useful in the treatment of different ailments including urinary diseases. Today, it is also used worldwide for the treatment of skin ailments by way of depigmenting, which means that arbutin is a component of many products in the cosmetics and healthcare industries. It is also relevant in the food industry. Hundreds of publications have appeared describing the isolation, structure determination, toxicology, synthesis, and biological properties of arbutin as well as the molecular mechanism of melanogenesis (tyrosinase inhibition). This review covers the most important aspects with special emphasis on the chemical and biocatalytic methods for the production of arbutin.

In the title compound, C16H14O, the cyclohexene ring has a half-chair conformation. The mean plane, calculated through all non-H atoms of the molecule, except for the central CH2 atoms of the cyclohexene ring, which deviate by 0.340 (3) and −0.369 (3) Å from this mean plane, has an r.m.s. deviation of 0.012 Å. In the crystal, there are C—H...π contacts present, resulting in the formation of zigzag chains propagating along the [010] direction.