Kinetic model of metabolic network for xiamenmycin biosynthetic optimisation

• Published in: IET systems biology 2016-02, Vol.10 (1), p.17-22
• Main Authors: Xu, Min-juan, Chen, Yong-cong, Xu, Jun, Ao, Ping, Zhu, Xiao-mei
• Format: Article
• Language: English
• Subjects: antifibrotic bioactivity; bacterium; Benzopyrans; biochemistry; Bioengineering; Carbon; carbon sources; citric acid cycle; enzymes; flux distributions; Fluxes; generic enzymatic rate equations; genetics; Glucose; glycerol; Glycerols; kinetic metabolic model; kinetic model; Kinetics; Lyapunov function; Lyapunov methods; mangrove‐derived Streptomyces xiamenensis; Mathematical models; metabolic network; Metabolic Networks and Pathways; microorganisms; Models, Biological; Networks; optimisation; Optimization; pharmaceuticals; phosphoenolpyruvate synthesis; prenylated benzopyran compounds; S. lividans; Special Issue based on the 8th International Conference on Systems Biology and the 4th Translational Bioinformatics Conference (ISB/TBC2014); Streptomyces - metabolism; Streptomyces lividans; Systems Biology; Threonine - analogs & derivatives; Threonine - biosynthesis; xiamenmycin biosynthetic optimisation; xiamenmycin production; xiamenmycin‐oriented genetic modification
• ISSN: 1751-8849; 1751-8857
• DOI: 10.1049/iet-syb.2014.0054

Xiamenmycins, a series of prenylated benzopyran compounds with anti-fibrotic bioactivities, were isolated from a mangrove-derived Streptomyces xiamenensis. To fulfil the requirements of pharmaceutical investigations, a high production of xiamenmycin is needed. In this study,, the authors present a kinetic metabolic model to evaluate fluxes in an engineered Streptomyces lividans with xiamenmycin-oriented genetic modification based on generic enzymatic rate equations and stability constraints. Lyapunov function was used for a viability optimisation. From their kinetic model, the flux distributions for the engineered S. lividans fed on glucose and glycerol as carbon sources were calculated. They found that if the bacterium can utilise glucose simultaneously with glycerol, xiamenmycin production can be enhanced by 40% theoretically, while maintaining the same growth rate. Glycerol may increase the flux for phosphoenolpyruvate synthesis without interfering citric acid cycle. They therefore believe this study demonstrates a possible new direction for bioengineering of S. lividans.