Low molecular weight protein tyrosine phosphatases control antibiotic production in Streptomyces coelicolor A3(2)

Streptomyces coelicolor A3(2) possesses a low molecular weight protein tyrosine phosphatase (LMW-PTP),PtpA, that affects the production of undecylprodigionsin (RED) and actinorhodin (ACT). In this study we identifiedanother LMW-PTP called sco3700. Tyrosine phosphatase activity of the purified Sco3700 was established usingpara-nitrophenyl phosphate and the tyrosine-phosphorylated protein PtkA from Bacillus subtilis as substrates. Theoptimum pH for the Sco3700 phosphatase activity was 6.8, and K_M for pNPP was 14.3 mM compared to pH 6.0and K_M0.75 mM for PtpA. The potential of Sco3700 to participate, alongside PtpA  Ppppdaspo, in the regulation of S. coelicolorantibiotic production was investigated. Hence, S. coelicolor A3(2) strains with ptpA and sco3700 overexpressionwere constructed and characterized for growth, RED and ACT production. We did observe an increase in volumetricproductivity of ACT in the ptpA over expression strain. Furthermore, a significantly earlier onset of ACT productionwas observed when ptpA was over expressed. Sco3700 overexpression had a pleiotropic effect on the cell, and thestrain exhibited lower productivities and final concentrations of antibiotics. We conclude that Sco3700 is indeed atyrosine phosphatase, and it contributes to regulation of antibiotic production in S. coelicolor affecting the timing ofonset of the antibiotic production