Enzymatic Reconstitution and Biosynthetic Investigation of the Lasso Peptide Fusilassin.

ABSTRACT: Lasso peptides are a class of ribosomally synthesized and post-translationally modified natural product which possess a unique lariat knot conformation. The low entropy "threaded" conformation endows lasso peptides with considerable resistance to heat and proteolytic degradation, which are attractive properties for the development of peptide-based therapeutics. Despite their discovery nearly 30 years ago, the molecular mechanism underlying lasso peptide biosynthesis remains poorly characterized due to the low stability of the purified biosynthetic enzymes. Here, we report the biosynthetic reconstitution of a lasso peptide derived from Thermobifida fusca, termed fusilassin. Beyond robust catalytic activity, the fusilassin enzymes demonstrate extraordinary substrate tolerance during heterolo

SUBMITTER: DiCaprio AJ 

PROVIDER: S-EPMC7368380 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature