Deep-Sea Genome Mining Reveals Cooperative ATP-Grasp Ligase-Directed Biosynthesis of Pentacyclic Myxomiditides with Potent Protease Inhibition.

ABSTRACT: Microviridins are ribosomally synthesized and post-translationally modified peptides, typically featuring a conserved tricyclic structure formed by two ATP-grasp ligases. However, the diversity and evolution of these enzymes remain incompletely understood. Here, we identify a distinct ATP-grasp ligase subclade (MyxF) that specifically modifies the conserved (KxxE)_n motif, defining a new subclass of microviridins with the (KxxE)_nTxKxPSDx-(D/E)-(D/E) sequence signature. Guided by SSN analysis, we discovered a deep-sea myx biosynthetic gene cluster from 10,000 m sediments and heterologously expressed two pentacyclic microviridin-like peptides, Myxomiditide A and B. Using mass spectrometry and NMR, we fully elucidated their chemical structures, revealing not only t

SUBMITTER: Li Y 

PROVIDER: S-EPMC12848669 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature