Fachbereiche | |
---|---|
Buchreihen (90) |
1260
|
Geisteswissenschaften |
2246
|
Naturwissenschaften |
5309
|
Mathematik | 223 |
Informatik | 310 |
Physik | 971 |
Chemie | 1346 |
Geowissenschaften | 130 |
Humanmedizin | 241 |
Zahn-, Mund- und Kieferheilkunde | 10 |
Veterinärmedizin | 98 |
Pharmazie | 147 |
Biologie | 812 |
Biochemie, Molekularbiologie, Gentechnologie | 114 |
Biophysik | 25 |
Ernährungs- und Haushaltswissenschaften | 44 |
Land- und Agrarwissenschaften | 992 |
Forstwissenschaften | 202 |
Gartenbauwissenschaft | 18 |
Umweltforschung, Ökologie und Landespflege | 145 |
Ingenieurwissenschaften |
1713
|
Allgemein |
91
|
Leitlinien Unfallchirurgie
5. Auflage bestellen |
Inhaltsverzeichnis, PDF (57 KB)
Leseprobe, PDF (210 KB)
ISBN-13 (Printausgabe) | 9783954049608 |
ISBN-13 (E-Book) | 9783736949607 |
Sprache | Englisch |
Seitenanzahl | 128 |
Umschlagkaschierung | matt |
Auflage | 1. Aufl. |
Buchreihe | Hochschulschriften - Institut für Systembiotechnologie, Universität des Saarlandes |
Band | 4 |
Erscheinungsort | Göttingen |
Erscheinungsdatum | 13.07.2015 |
Allgemeine Einordnung | Dissertation |
Fachbereiche |
Mikrobiologie und Biotechnologie
|
Schlagwörter | violacein, deoxyviolacein, Escherichia coli, metabolic engineering |
Violacein and deoxyviolacein are promising therapeutics against pathogenic bacteria and viruses as well as tumor cells. In the present work, systems-wide metabolic engineering was applied to Escherichia coli for heterologous production of these high-value products. First, a high performance liquid chromatography method for accurate separation and quantification of violacein and deoxyviolacein was developed. Afterwards, a basic producer, E. coli dVio-1, that expressed the vioABCE cluster from Chromobacterium violaceum under control of the araBAD promoter and induction by L-arabinose, was constructed. Targeted intracellular metabolite analysis then identified bottlenecks in pathways that supply tryptophan, the major product building block of the natural products of interest. This was used for systems-wide engineering of serine, chorismate and tryptophan biosynthesis and the non-oxidative pentose-phosphate pathway, followed by elimination of L-arabinose catabolism. Transferred to a glycerol-based fed-batch process, E. coli dVio-8 surpassed the gram scale and produced 1.6 g L-1 deoxyviolacein (> 99.5% purity). The created chassis of a high-flux tryptophan pathway was complemented by genomic integration of the vioD gene of Janthinobacterium lividum, which enabled exclusive production of violacein (710 mg L-1 with 99.8% purity). This demonstrates the potential of E. coli as a platform for production of tryptophan based therapeutics.