Systems metabolic engineering for the production of bio‐nylon precursor

Systematic approaches for in silico design of metabolic pathways and experimental evaluation of cellular performance are important for the development of industrially useful organisms. In this issue of Biotechnology Journal, Buschke et al. [1] report the production of 1,5-diaminopentane using xylose produced by Corynebacterium glutamicum by employing integration methodologies of rational design for genetic improvement, experimental analysis of metabolic fluxes, and comprehensive gene expression. Recent progress in 'omics sciences has facilitated the analysis of microorganisms for molecular breeding. There has been increasing interest for the integration of in silico and experimental approaches for the development of microbial cells for industrial applications. In silico simulations aid the rational design of metabolic pathways for the production of target compounds. On the basis of the in silico simulation data, the host organism is genetically manipulated to improve target metabolite production [2, 3]. The 13C-metabolic flux analysis method is useful for determining the flux distribution; this method requires experimental data procured from genetically manipulated strains [4, 5]. Identification of the genes that confer useful phenotypes for cells on the basis of DNA microarray analysis is also important [6]. The integration method, which combines in silico and experimental approaches for the development of cell factories is shown in Fig. 1. Many applications of the integration method for the bioproduction of chemicals and fuels have been reported [7, 8]. Concept of systems metabolic engineering. Production of 1,5-diaminopentane, a bio-nylon precursor, is reported by Buschke et al. [1], in this Special Issue “Systems Metabolic Engineering” of Biotechnology Journal. Buschke et al.'s study [1] is a good example of the successful application of bioengineering that contributes to the recent progress in systems metabolic engineering. Diaminopentane is produced by a one-step reaction from lysine by C. glutamicum, which is a well-known amino acid-producing bacterium and has recently used for chemical production as well [9, 10]. The authors have previously developed a high-producing strain that converts glucose to diaminopentane [11]. In the current study [1], a novel strain which produces diaminopentane from xylose was developed. Xylose utilization is particularly useful because xylose is a main component of lignocellulose waste, which is widely available. The previously developed diaminopentane-producing strain, DAP-Xyl1, produce diaminopentane less efficiently from xylose than from glucose. Thus, Buschke et al. [1] apply a systematic approach to improve diaminopentane production. In silico elementary flux mode analysis predicts an ideal metabolic state for diaminopentane production. The theoretical maximum yield from xylose is predicted, and the analysis reveal that the high oxidative pentose phosphate pathway (PPP) flux and the zero flux of the tricarboxylic acid (TCA) cycle are important for diaminopentane production; however, the metabolic flux of these pathways in the strain DAP-Xyl1 does not show good agreement with ideal metabolic flux for diaminopentane production. The small flux of PPP and the large flux of the TCA cycle cause low production of diaminopentane by the strain DAP-Xyl1. Additionally, gene selection is performed on the basis of the transcriptome analysis results. The novel, rationally designed strain DAP-Xyl2 successfully produce more than 100 g/L of diaminopentane after 75 h of cultivation. This study demonstrates the development process of a high performance strain of C. glutamicum and the importance of systems metabolic engineering approach for developing an industrially useful microorganism [7, 12]. The author declares no conflict of interest.