Post-translational modification in microviridin biosynthesis.

Area of Science:

• Biochemistry
• Microbiology
• Natural Product Chemistry

Background:

• Cyanobacteria are significant sources of bioactive natural products, particularly nonribosomal peptides and polyketides.
• Microviridins are a class of peptidase inhibitors produced by cyanobacteria.

Purpose of the Study:

• To elucidate the post-translational modification pathway of microviridin K, a novel microviridin.
• To characterize the enzymes involved in microviridin K biosynthesis.
• To investigate the distribution of microviridin biosynthesis genes in bacteria.

Main Methods:

• Over-expression of three key enzymes from the microviridin (mvd) biosynthetic gene cluster.
• In vitro biochemical assays including chemical degradation and mass spectrometry.
• In silico analysis of the mvd gene cluster.

Main Results:

• Demonstrated that RimK homologues MvdD and MvdC catalyze ester and amide bond formation, respectively.
• Showed that these cross-linking reactions are crucial for converting a linear precursor peptide into the mature, tricyclic microviridin K.
• Identified the complete six-gene mvd biosynthetic gene cluster in P. agardhii.

Conclusions:

• The post-translational modification pathway for microviridin K involves sequential cross-linking by MvdD and MvdC.
• The mvd gene cluster provides a blueprint for microviridin biosynthesis.
• Microviridin-like compounds may be widespread in bacteria based on in silico analysis.