Substrate Specificity and Scope of MvdD, a GRASP-like Ligase from the Microviridin Biosynthetic Gene Cluster

• DOI: 10.1021/cb900088r
• Publication Date: 2009-05-18T13:42:31Z
• Authors: Benjamin Philmus; Joshua P. Guerrette; Thomas K. Hemscheidt
• Keywords: Gene cluster

The cyanobacterial protease inhibitor microviridin K is ribosomally biosynthesized as a prepeptide (MvdE) and subsequently modified posttranslationally by double lactonization followed lactamization. Two proteins belonging to the GRASP superfamily of ligases catalyze these ring closures. We here show that one (MvdD) forms lactones in specific order, larger being formed first, size requirement for both lactonizations stringent. However, first cyclization MvdD accepts alanine substitution all C-terminal positions are not directly involved cross-linking, whereas second dependent on presence residues MvdE. This suggests possesses some, albeit limited, substrate tolerance might be useful modification peptides group metabolites.