Streptolydigin inhibits RNA synthesis by binding to RNA polymerase and does not inhibit eukaryotic RNA polymerases. Streptolydigin is a 3-acetyltetramic acid antibiotic and a potent bacterial RNA polymerase inhibitor (Ki: 18 μM and a Kd: 15 μM).

RNA polymerase (bacterial):（ki）18 μM

Streptolydigin inhibits initiation, elongation, and pyrophosphorolysis by bacterial RNA polymerase. Streptolydigin inhibits T. thermophilus RNA polymerase (a Ki: 1.8 μM). Binding of Streptolydigin to RNA polymerase strictly depends on a noncatalytic magnesium ion which is likely chelated by the aspartate of the bridge helix of the active center. Streptolydigin interacts with three structural elements within RNAP: the Stl pocket, the bridge helix, and the trigger-loop region. The Streptolydigin streptolol moiety interacts with the Streptolydigin pocket and bridge helix, and the Streptolydigin tetramic-acid moiety interacts with the trigger-loop region [1][3].