Amycolatopsis balhimycina

Infection caused by methicillin-resistant Staphylococcus aureus (MRSA) is an increasing societal problem. Typically treatments of these infections can only be done with the glycopeptides antibiotics vancomycin, synercid, and teiocoplanin. Amycolatopsis balhimycina serves as a model strain for glycopeptide production due to its ability to produce the vancomycin-analogue balhimycin. The balhimycin yield obtained by A. balhimycina is, however, low and there is therefore a need to improve balhimycin production by this organism and this may also lead to a wider use of this organism as a model for glycopeptide production. With the objective to improve the knowledge base of this organism, we therefore performed genome-sequencing of A. balhimycina and used these data to reconstruct a genome-scale metabolic model for the organism. We generated an almost complete A. balhimycina genome sequence comprising 10,562,587 base pairs assembled in 2,153 contigs. The high GC-genome (~69%) included 8,585 open reading frames (ORFs). We used our integrative toolbox called SEQTOR for gene annotation, and used annotated genes to reconstruct a genome-scale metabolic network of A. balhimycina. In the model reconstruction we also used biochemical information retrieved from pathway databases, biochemistry textbooks and recent publications. The resulting network contained 583 ORFs as protein encoding genes (7% of the predicted 8,585 ORFs), 407 EC numbers, 647 metabolites and 1,363 metabolic reactions. During the analysis of the metabolic model, linear, quadratic and evolutionary programming problems using Flux Balance Analysis (FBA), Minimization Of Metabolic Adjustments (MOMA) and OptGene were applied and phenotypic behavior and improved balhimycin production were simulated. The model showed a good agreement between in silico data and experimental data and also identified key reactions associated with increased balhimycin production. The reconstruction of the genome-scale metabolic model of A. balhimycina serves as a basis for physiological characterization. The model allows a rational design of engineering strategies for increasing balhimycin production in A. balhimycina and glycopeptide production in general(1).

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Amycolatopsis balhimycina model
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Citations
1) W. Vongsangnak*, L.F. Figueiredo*, J. Forster. T. Weber, J. Thykaer, E. Stegmann, W. Wohlleben and J. Nielsen (2011) Genome-Scale Metabolic Representation of Amycolatopsis balhimycina -
A * indicates that these authors contributed equally to the work.