Skip to ContentSkip to Navigation
About usFaculty of Science and EngineeringResearchGRIPNews and activities

Exploiting catalytic promiscuity for biocatalysis

01 June 2015

Carbon-carbon bond formation by a proline-based tautomerase

A powerful theme that is highly relevant to the design of new biocatalysts is that of catalytic promiscuity, where an enzyme catalyzes alternative reactions in addition to its biologically relevant one. Enzyme promiscuity has great promise as a source of synthetically useful catalytic transformations. Because most enzyme active sites provide a constellation of potential catalytic groups that can act as acids, bases, and nucleophiles, the promiscuity of enzymes is likely to be widespread and tightly linked to the “chemical potential” of their active sites. Here lie formidable challenges and possibilities: the use of mechanistic reasoning to discover new promiscuous activities in existing enzymes, which could be exploited as starting points to generate novel biocatalysts.

Yufeng Miao investigated whether the enzyme 4-oxalocrotonate tautomerase (4-OT) exhibits catalytic promiscuity for carbon-carbon bond-forming reactions. 4-OT naturally catalyzes enol-keto tautomerization reactions, and is characterized by a unique catalytic N-terminal proline. Based on the presence of a nucleophilic proline in 4-OT’s active site, it was predicted and discovered that 4-OT can catalyze the Michael-type addition of aliphatic aldehydes to a wide variety of nitroolefins. The resulting γ-nitroaldehydes are important precursors for γ-aminobutyric acids, such as the marketed pharmaceuticals phenibut (tranquilizer), baclofen (anti-alcoholic), and pregabalin (anticonvulsant). 4-OT was also found to catalyze challenging inter- and intramolecular aldol reactions.

The outcomes of his work may support an exciting area in protein engineering research as the newly discovered promiscuous activities of 4-OT can serve as crucial starting points for the laboratory evolution of novel biocatalysts for carbon-carbon bond formation.

PhD ceremony:

When:

June 05, 2015

Start:

14:30

Promotors:

prof. dr. G.J. (Gerrit) Poelarends , prof. dr. W.J. (Wim) Quax

Where:

Academy building RUG

Faculty:

Mathematics and Natural Sciences

Yufeng Miao
Yufeng Miao
Last modified:02 June 2015 12.35 p.m.
printView this page in: Nederlands

More news

  • 15 May 2019

    Academy Medal for Trudy Dehue

    Trudy Dehue, scientific sociologist, author and emeritus professor of the University of Groningen, will receive the Academy Medal from the Royal Netherlands Academy of Arts and Sciences (KNAW). The Academy Medal is awarded every other year to individuals...

  • 15 May 2019

    Van Rijn advice hits UG hard

    The advice from the Van Rijn committee concerning the funding of higher education has heavy consequences for the UG as a broad-based classical university. The proposed redistribution of funds in favour of technical sciences is at the expense of degree...

  • 14 May 2019

    Number of children with type 1 diabetes doubled

    The number of children who are annually diagnosed with type 1 diabetes has doubled over the last 30 years. This is one of the conclusions of the PhD thesis written by Angelien Spaans-Hummelink, who works as a paediatrician at the diabetes clinic at...