Analysis of the metabolism of Corynebacterium glutamicum and pathway engineering for alternative substrate utilization and production of industrially relevant metabolites

 

Corynebacterium glutamicum is a facultative anaerobic, Gram-positive organism that grows on a variety of sugars, organic acids and alcohols and is widely used in the industrial production of L-amino acids, particularly L-glutamate and L-lysine. Our interest is to identify and analyze those central metabolic enzymes and pathways which are responsible for amino acid production by C. glutamicum. Here we are particularly interested in the biochemistry and regulation of those enzymes and reactions which are centered at the so-called PEP-pyruvate-oxaloacetate node and involved in precursor supply for L-glutamate, L-lysine and L-valine production (for reviews see Sauer & Eikmanns 2005; Bott & Eikmanns 2012). A further aim is the identification and characterization of regulatory genes and proteins involved in the control of carbon utilization and of glycogen metabolism, and the regulatory mechanisms (for reviews see Eikmanns 2005; Arndt & Eikmanns 2008). Highlights of our research include the characterization of acetate, ethanol and arabitol metabolism of C. glutamicum (Gerstmeir et al. 2003, Arndt et al. 2008; Laslo et al. 2012), the identification and biochemical and genetic characterization of pyruvate-converting enzymes (Schreiner & Eikmanns 2005; Schreiner et al. 2005; 2006; Klaffl & Eikmanns, 2010) and of enzymes involved in glycogen metabolism (Seibold et al. 2007a, 2007b, 2009, 2010, 2011; Seibold & Eikmanns 2013) and the identification and characterization of three novel transcriptional regulators involved in acetate metabolism (Gerstmeir et al. 2004; Cramer et al. 2006; Cramer and Eikmanns 2007; Cramer et al. 2007; Auchter et al. 2010; Auchter et al. 2011a) and in central carbon metabolism (Emer et al. 2009; Auchter et al. 2009, 2011b; Klaffl et al. 2013). Moreover, C. glutamicum strains tailored for high yield L-valine, pyruvate, succinate, 2-ketoisovalerate, 2-ketoisocaproate and isobutanol production have been developed  and analyzed (Blombach et al. 2007, 2008, 2009; Bartek et al. 2010a, 2010b, 2011; Wieschalka et al. 2012, 2013; Krause et al. 2010; Blombach et al. 2011; Bückle-Vallant et al. 2014; Eikmanns and Blombach 2014a, b, c; Oldiges et al. 2014).