Visual screening of PGP-1 inhibitors and identification of intestinal microbiota with active PGP-1 using a NIR fluorescent probe

Pyroglutamyl aminopeptidase I (PGP-1) from intestinal microbiota is known as a hydrolase, specifically for degradation of L-pyroglutamate (L-pGlu) residue from the amino terminus of L-pGlu proteins, peptides, and synthetic analogues. In the present work, an enzyme-activated NIR fluorescent probe (ADMP) with a remarkable Stokes shift has been developed for PGP-1 assay. Using a high-throughput screening method based on detecting ability of ADMP, several potent inhibitors such as menadione, alantolactone, constunolide and carnosic acid were obtained toward PGP-1 from natural compounds library. Additionally, under the guidance of fluorescence sensing of endogenous PGP-1 using ADMP as a NIR sensor, a intestianl bacterium (Klebsiella pneumoniae strain 1557) and a saccharomycete (Trichosporon asteroids) repsectively, were efficiently identified from human feces, which were expected to play an important role for regulating L-pGlu-constituents metabolism in gut.