Artificial Metalloenzymes: augmenting biological synthesis with chemical versatility

Samenvatting

The global aim of this program is to augment bio-synthesis with ?non-natural chemistry? by integration of artificial metalloenzymes into bio-synthetic pathways in cells, for the sustainable synthesis of molecules with novel structures.
Two promising new classes of novel, cell-comparible, artificial metalloenzymes, based on a transcription factor, will be used:
" Class A relies self-assembly of the artificial metalloenzyme by supramolecular anchoring of a metal catalyst in a hydrophobic pocket of the transcription factor.
" Class B involves ribosomal incorporation of non-proteinogenic amino acids containing a metal binding ligand, using expanded code methodology
This proposed program consists of two subprojects that are of key importance for achieving the global aim of this proposal, but also represent important milestones for the field in their own right.
I. Structure based design and evolution of artificial metalloenzymes for novel catalytic chemistry in vitro. These will then be applied to novel reactions that have no equivalent in ?conventional? catalysis and/or biology, such as asymmetric hydrations and reactions with ammonia, which are unsolved problems in chemistry
II. Augmenting biosynthesis with non-natural chemistry by integrating artificial metalloenzymes in cells. Artificial metalloenzymes will be used in cells to (i) functionalize enoyl-CoA esters in a non-natural Friedel-Crafts alkylation reaction with indole and (ii) for in vivo derivatization of Nisin, providing rapid access to novel compounds that can be screened directly as antibiotics.
In this highly ambitious project, the emerging field of artificial metalloenzymes will start to address real challenges, such as ?difficult? transformations and integration with biological synthesis. Thus, this program will contribute greatly to the goal of making chemistry more sustainable and will open up new avenues in the fields of catalysis and synthetic biology.

Producten

Wetenschappelijk artikel

Kenmerken

Projectnummer

724.013.003

Hoofdaanvrager

Prof. dr. J.G. Roelfes

Verbonden aan

Rijksuniversiteit Groningen, Faculty of Science and Engineering (FSE), Stratingh Instituut voor Chemie

Uitvoerders

A.J.E. Borg, S. Chordia, Dr. S. Hernández Mejías, Dr. C. Mayer, Dr. E. Reddem, Dr. E. Reddem, Prof. dr. J.G. Roelfes, Dr. L. Villarino Palmaz

Looptijd

01/07/2014 tot 30/06/2019