Work

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

Year: 2025

Type: article

Abstract: 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 . • CdgA, a bifunctional c -di-GMP-metabolizing enzyme from Streptomyces ghanaensis. • CdgA shows heme-dependent and oxidation-state-dependent activity changes. • Without a heme cofactor CdgA is only able to degrade c -di-GMP. • In the heme-bound Fe(II) form it is also able to synthesize c -di-GMP.

Source: Journal of Inorganic Biochemistry

DOI: 10.1016/j.jinorgbio.2025.112874

Authors: Olaf Latta, Emily E. Weinert, Andreas Bechthold

Institutions: University of Freiburg, Pennsylvania State University

Language: English

Topic: Bacterial biofilms and quorum sensing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,220

Funders: National Science Foundation, Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg