چکیده انگلیسی مقاله |
Objective and background Rhamnolipids (RLs): Rhamnolipids belong to one of the most outstanding groups of studied microbial surfactants (glycolipids) with specific properties such as low toxicity, high biodegradability and antimicrobial effects. These characteristics made them suitable agents with plentiful supply of applications in diverse fields (i.e. environmental protection, food industries, cosmetics and household detergents, and medical uses especially for burn wound healing) (Tiso et al., 2017). They are mainly produced by different strains of Pseudomonas aeruginosa, the opportunistic human pathogen. Their production is highly regulated by two hierarchically-arranged complex quorum-sensing systems (Las and Rhl). RLs are secondary metabolites comprised of two different moieties: a hydrophilic head (rhamnose) and a hydrophobic tail (3-(hydroxyalkanoyloxy) alkanoic acid (HAA)). Their main precursors are synthesized through altered pathways of metabolic network far from each other (dTDP-L-rhamnose is synthesized from D-glucose-6-phasphate either through gluconeogenesis or Entner-Doudoroff pathway, while HAA is produced from Acetyl-CoA through fatty acid de novo synthesis) (Henkel et al., 2017). Heterologous production of RLs: For industrial RLs production, the use of P. aeruginosa would be excessively problematic. Hence, the safe and proper member of Pseudomonas family, P. putida, known as an industrial work-horse, has been considered as a promising candidate for heterologous RLs biosynthesis owing to existence of similar associated metabolic pathways. However, since RLs are inherently growth-uncoupled bioproducts, the heterologous RLs biosynthesis yield in P. putida is not satisfactorily high (Kahlon, 2016). Systems biology application for direction of metabolic engineering: To enhance the RLs production yields, better understanding of Pseudomonas metabolism at the systems level is required taking simultaneously the different pathways responsible for synthesis of the both RLs moieties into consideration. Accordingly, metabolic systems biology along with its proficient tools such as genome-scale metabolic network reconstructions (GENREs) and constraint-based genome-scale models (GEMs) play fundamental roles. Also, employing the capable in silico algorithms may contribute to classifying the appropriate opportunities for systems metabolic engineering and, if probable, growth-coupled RLs biosynthesis (Lewis et al., 2012; Lee et al., 2012). In the current study, a novel bottom-up systems biology approach is applied to identify the reciprocal genes responsible for simultaneous biomass and RLs formation in Pseudomonas bacteria based on beneficial GENREs developed for P. aeruginosa and P. putida (Yen et al., 2015). a few reciprocal genes belong to a few effective subsystems are responsible for simultaneous growth and RLs biosynthesis. |