## Materials and Methods
### Assay of Extracellular and Intracellular Actinorhodin (ACT) Production  
The strains _S. lividans ppk::May, S. lividans pptA_IFD deletion mutant, and _S. coelicolor_ M145 were grown for 72 h at 28 \({}^{\circ}\)C. Each strain was grown on four individual 9 mm diameter plates (Figure 4b) or on four 5 mm diameter plates (Figure 4c) of solid R2 YE medium with no KH\({}_{2}\)PO\({}_{4}\) added but containing 1 mM free K\({}_{2}\)HPO\({}_{4}\) from elements of the media (condition of phosphate limitation). To quantify extracellular ACT, at different points throughout growth, the cellophane of the 9 mm diameter plates was lifted and a agar cylinder of the growth medium was taken aseptically from each of the four replicates using an appropriate device (Figure 4b) or the totality of the agar medium present just under the cellophane disk cellophane of each of the 4 replicates was cut into small pieces (Figure 4c). The 4 agar cylinders together (Figure 4b) or the agar pieces (Figure 4c) were allowed to diffuse in 2 mL of water for 2 h at 4\({}^{\circ}\)C. The first eluate was transferred into a new tube. The operation was repeated twice and 3 mL of HCl (3 M) were added to the 6 mL of final eluate. The mixture was incubated on ice for one night to allow ACT precipitation. To quantify intracellular ACT at different time points throughout growth (Figure 4b) or after 72 h of cultivation (Figure 4c), mycelium present in an area of 1 cm\({}^{2}\) of each replicate (Figure 4b) or the totally of the mycelium present under the cellophane disk (Figure 4c), was scraped off, lyophilized, and weighted. Collected mycelium samples were incubated in 1 mL of KOH (1 M) for 30 mn at 4 \({}^{\circ}\)C under agitation. After centrifugation, the supernatant was transferred into a new tube and this operation was repeated five times. Two mL of HCI (3 M) were added to the 4 mL of final eluate. The mixture was incubated on ice one night to allow ACT precipitation. After centrifugation at 13,000\(\times\)_g_ for 30 mn at 4 \({}^{\circ}\)C and elimination of the supernatant, the reddish pellet of precipitated ACT was re-suspended in 1 mL KOH (1 M). The optical density of the KOH solutions corresponding to extra- and intra-cellular ACT was determined at 640 nm in a Shimadzu UV-1800 spectrophotometer using KOH (1 M) as blank. The Beer-Lambert law (molar attenuation coefficient of ACT = 25,320) was used to calculate the amount of ACT produced expressed in nano moles per mg of dry biomass [43]. For Figure 4c, the results obtained are presented as the mean \(\pm\) standard error; a _p_-value < 0.05 was considered as statistically significant. The letters above the histograms indicate the significance of the differences. When two histograms bear two different letters that means that they are statistically significantly different (_p_ > 0.05; Tukey adjusted comparisons). For Figure 4b, the standard error could not be presented since the 4 agar plugs, as the four mycelial samples, were incubated in the same tube. Determination of Total Lipid Content Using Attenuated Total Reflectance-Fourier Transform Infra Red Spectroscopy (ATR-FTIRS) Measurements  
In order to determine total lipid content of the strains grown in the same conditions as above (Figure 5), lyophilized mycelial samples were subjected to FTIR spectroscopy using a Bruker Vertex 70 FTIR spectrophotometer with a diamond ATR attachment (PIKE MIRacle crystal plate diamond ZnSe) and a MCT detector with a liquid nitrogen cooling system as described previously [52]. The total lipid content of the strains expressed first in arbitrary units, was converted into \(\upmu\)g of fatty methyl esters (FAME) per mg of dry mycelium using the converting equation previously established [53; 54]. Comparative Proteomic Analysis of the Wild Type Strain of S. lividans and of the \(\Delta\)SLI_4383 Mutant  
Total protein extracts of thirty two samples resulting from four biological replicates of _S.