Heme dependent activity of the Streptomyces c-di-GMP-metabolizing enzyme CdgA

Streptomyces species are vital for producing natural products like antibiotics, with c-di-GMP playing a key role in regulating processes such as differentiation. C-di-GMP metabolism is controlled by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), which synthesize and hydrolyze c-di-GMP, respectively, to modulate cellular levels. To improve our understanding of c-di-GMP-regulated processes in Streptomyces, we have characterized a c-di-GMP-metabolizing enzyme CdgA from Streptomyces ghanaensis that contains both a diguanylate cyclase and a phosphodiesterase domain. Our studies demonstrate that the enzyme is purified in a form without heme and is only able to degrade c-di-GMP. When reconstituted with heme, it enables c-di-GMP synthesis, and depending on the redox state the synthesis rate is changed. To our knowledge, this is the first heme-dependent activity reported for a c-di-GMP-metabolizing enzyme in Streptomyces and has major implications for understanding the way c-di-GMP is metabolized in vivo in Streptomyces.