PhD defence J.L. Zhang
|When:||Mo 26-08-2019 11:00 - 12:00|
Biocatalytic asymmetric hydroamination by native and engineered carbon-nitrogen lyases
New enzymes to prepare amino acid precursors to pharmaceuticals and food additives
The work described in the thesis of Jielin Zhang sets the stage for further development of practical biocatalytic processes for the more sustainable and step-economic synthesis of an important class of aminocarboxylic acids.
Unnatural amino acids are important compounds with wide-ranging applications in the pharmaceutical and nutraceutical industry. Due to their broad application in the development of drugs and food additives, various chemical methods have been developed for the asymmetric synthesis of enantiomerically pure unnatural amino acids. Biocatalysis, which involves the use of enzymes or microorganisms to accelerate chemical reactions, represents a complementary sustainable approach for preparation of unnatural amino acids. Modern tools of protein discovery and engineering as well as advances in molecular biology and protein structure determination support the development of new biocatalysts and their integration into industrial processes.
Zhang explored the synthetic usefulness of two carbon-nitrogen lyases for the production of a wide variety of valuable L-aspartic acid derivatives. In her PhD thesis, she describes the identification and mechanistic and structural characterization of a new carbon-nitrogen lyase, named ethylenediamine‑N,N’‑disuccinic acid lyase (EDDS lyase), which was shown to possess a very broad substrate scope. With the use of this fascinating enzyme, as well as a previously reported 3-methylaspartate ammonia lyase (MAL), a very large collection of difficult L-aspartic acid derivatives was prepared via enantioselective hydroamination of fumaric acid. These enzymatic reactions were further incorporated into multienzymatic and chemoenzymatic cascades, yielding valuable biologically active compounds, including important metallo-β-lactamase inhibitors and vitamin B5 derivatives. Also, structure-inspired engineering of EDDS lyase was performed, generating a tailor-made biocatalysts for the selective synthesis of precursors to low-calorie artificial dipeptide sweeteners.
Promotores: Prof.dr. G.J. Poelarends en Prof.dr. W.J. Quax