Fig. 5

Visualisation of differences in glycolysis, TCA-cycle, valine metabolism and erythromycin biosynthesis at three omics levels. Presented data is from fermentation time point t2. Node (label) legend: circle: gene (locus tag), blue rectangle: protein (protein name), yellow octangle: metabolite (metabolite name). Circle centre and rim colours represent log2 (fold change between HP and WT) for gene and protein expression, respectively (see colour key). A red arrow next to a circle indicates upregulation in our 2D gel experiment, and a green arrow indicates downregulation. Gene mutations in the HP strain are indicated by magenta coloured gene labels. The inset shows a schematic representation of the proposed changes in metabolic flow between HP and WT strains. In the HP strain, key points of entry into the TCA cycle are likely restricted due to downregulation of pdh, sdh, and fdh (shown as thin red lines). Combined with the upregulation of ilvB, this could divert the flow of metabolites towards the biosynthesis/degradation pathway of branched-chain amino acids (shown as thick blue lines), resulting in increased supply of methylmalonyl-CoA and propionyl-CoA, key precursors for erythromycin synthesis