Overexpression of adenylation domains for the identification of the biosynthetic pathway of K-26, an ACE inhibiting metabolite
Sease, Andrea Monique
K-26 is an acidic tripeptide molecule with ACE inhibitory activity. It represents one of three distinct classes of unique phosphonate containing compounds found in nature. Previous work has found that unlike other C-P bond containing compounds, its biosynthetic pathway does not contain the C-P bond forming enzyme PEP mutase, nor the CPEP mutase found exclusively in the Bialaphos biosynthetic pathway. Unique to this compound is the presence of the non-proteogenic amino acid moiety AHEP. Due to the interesting bioactivity associated with the presence of this moiety, work has been done to determine the origin of this molecule as well as to determine the origin of its bioactivity. After sequencing of the genome of the Actinomyces, sp. K-26 proteins of notable interest were over expressed and characterized. Adenylation domains were characterized, after expression, to determine selectivity.