99268-39-0Relevant articles and documents
β-Lactone formation during product release from a nonribosomal peptide synthetase
Schaffer, Jason E,Reck, Margaret R,Prasad, Neha K,Wencewicz, Timothy A
, p. 737 - 744 (2017/06/27)
Nonribosomal peptide synthetases (NRPSs) are multidomain modular biosynthetic assembly lines that polymerize amino acids into a myriad of biologically active nonribosomal peptides (NRPs). NRPS thioesterase (TE) domains employ diverse release strategies for off-loading thioester-tethered polymeric peptides from termination modules typically via hydrolysis, aminolysis, or cyclization to provide mature antibiotics as carboxylic acids/esters, amides, and lactams/lactones, respectively. Here we report the enzyme-catalyzed formation of a highly strained β-lactone ring during TE-mediated cyclization of a β-hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly line. The Obi NRPS (ObiF) contains a type I TE domain with a rare catalytic cysteine residue that plays a direct role in β-lactone ring formation. We present a detailed genetic and biochemical characterization of the entire Obi biosynthetic gene cluster in plant-associated Pseudomonas fluorescens ATCC 39502 that establishes a general strategy for β-lactone biogenesis.
Synthesis of (+)-Obafluorin, a β-Lactone Antibiotic
Lowe, Christopher,Pu, Yunlong,Vederas, John C.
, p. 10 - 11 (2007/10/02)
Optically pure obafluorin (1), an antibacterial agent from Pseudomonas fluorescens, was synthesized via lactonization of N--(2S,3R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid (6), which was prepared in a stereospecific manne
