title: Systems metabolic engineering of xylose-utilizing Corynebacterium glutamicum for production of 1,5-diaminopentane.
abstract: The sustainable production of industrial platform chemicals is one of the great challenges facing the biotechnology field. Ideally, fermentation feedstocks would rather rely on industrial waste streams than on food-based raw materials. Corynebacterium glutamicum was metabolically engineered to produce the bio-nylon precursor 1,5-diaminopentane from the hemicellulose sugar xylose. Comparison of a basic diaminopentane producer strain on xylose and glucose feedstocks revealed a 30% reduction in diaminopentane yield and productivity on the pentose sugar. The integration of in vivo and in silico metabolic flux analysis by (13) C and elementary modes identified bottlenecks in the pentose phosphate pathway and the tricarboxylic acid cycle that limited performance on xylose. By the integration of global transcriptome profiling, this could be specifically targeted to the tkt operon, genes that encode for fructose bisphosphatase (fbp) and isocitrate dehydrogenase (icd), and to genes involved in formation of lysine (lysE) and N-acetyl diaminopentane (act). This was used to create the C. glutamicum strain DAP-Xyl1 icd(GTG) Peftu fbp Psod tkt Δact ΔlysE. The novel producer, designated DAP-Xyl2, exhibited a 54% increase in product yield to 233 mmol mol(-1) and a 100% increase in productivity to 1 mmol g(-1) h(-1) on the xylose substrate. In a fed-batch process, the strain achieved 103 g L(-1) of diaminopentane from xylose with a product yield of 32%. Xylose utilization is currently one of the most relevant metabolic engineering subjects. In this regard, the current work is a milestone in industrial strain engineering of C. glutamicum. See accompanying commentary by Hiroshi Shimizu DOI: 10.1002/biot.201300097.
authors: Institute of Biochemical Engineering, Technische Universität, Braunschweig, Germany.
authors: Nele
authors: N
authors: Buschke
authors: Judith
authors: J
authors: Becker
authors: Rudolf
authors: R
authors: Schäfer
authors: Patrick
authors: P
authors: Kiefer
authors: Rebekka
authors: R
authors: Biedendieck
authors: Christoph
authors: C
authors: Wittmann
mesh_terms: D001426:Bacterial Proteins; D002103:Cadaverine / Q000032:analysis / Q000378:metabolism*; D002247:Carbon Isotopes / Q000378:metabolism; D048230:Corynebacterium glutamicum / Q000235:genetics / Q000378:metabolism*; D053263:Gene Regulatory Networks; D005947:Glucose / Q000378:metabolism; D007218:Industrial Microbiology; D026901:Membrane Transport Proteins; D060847:Metabolic Engineering / Q000379:methods; D053858:Metabolic Networks and Pathways; D049490:Systems Biology / Q000379:methods; D059467:Transcriptome; D014199:Trehalose / Q000378:metabolism; D014994:Xylose / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002247:Carbon Isotopes; D026901:Membrane Transport Proteins; D014994:Xylose; D014199:Trehalose; D005947:Glucose; D002103:Cadaverine