Enzymatic Cascade To Evaluate the Tricyclization of Glycopeptide Antibiotic Precursor Peptides as a Prequel to Biosynthetic Redesign

Natural products
are the greatest source of antimicrobial agents,
although their structural complexity often renders synthetic production
and diversification of key classes impractical. One pertinent example
is the glycopeptide antibiotics (GPAs), which are highly challenging
to synthesize due to their heavily cross-linked structures. Here,
we report an optimized method that generates >75% tricyclic peptides
from synthetic precursors in order to explore the acceptance of novel
GPA precursor peptides by these key existent biosynthetic enzymes.