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Streptomyces Clavuligerus Constraint-Based Modeling and Gene Expression Analysis for Clavulanic Acid Production

In this work, we use a high-resolution transcriptome of S. clavuligerus cultured on a chemically defined medium and the corresponding measured metabolic fluxes as experimental constraints to identify through an expanded genome-scale metabolic model the different metabolic process associated to primary/secondary metabolism based on available omics integration algorithms. The predicted fluxes showed to be in agreement with the corresponding gene expression data associated providing a detailed interpretation compared to traditional constrained-based methods (FBA and pFBA). In general, the observed patterns in intracellular fluxes coincided with reactions that have been identified as important precursors for secondary metabolism mainly those involved in clavulanic acid synthesis.