Figure 3.

Summary of link between guanosine metabolism and antibiotic production. During vegetative growth, cellular concentrations of GTP are high, but maintained by (p)ppGpp-mediated inhibition of GTP biosynthesis, most likely direct inhibition of GuaB. Under these conditions, c-di-GMP is produced, and it binds BldD to form a complex, which represses bld and whi genes. Under stress conditions, (p)ppGpp accumulates, resulting in efficient inhibition of GTP biosynthesis. However, high levels of (p)ppGpp also mediate an increase in Xdh production, averting excessive depletion of GTP. Reduced production of c-di-GMP results in derepression of bld and whi genes, leading to morphological differentiation. The accumulation of (p)ppGpp generally leads to production of secondary metabolites, including antibiotics. The role of BldD in antibiotic production remains to be fully elucidated.