The Experts below are selected from a list of 474 Experts worldwide ranked by ideXlab platform

Nein-chen Chang - One of the best experts on this subject based on the ideXlab platform.

Minruei Tsai - One of the best experts on this subject based on the ideXlab platform.

Bofong Chen - One of the best experts on this subject based on the ideXlab platform.

Chihching Cheng - One of the best experts on this subject based on the ideXlab platform.

Eshwar Mahenthiralingam - One of the best experts on this subject based on the ideXlab platform.

  • Genomics-driven discovery of a novel Glutarimide antibiotic from Burkholderia gladioli reveals an unusual polyketide synthase chain release mechanism.
    Angewandte Chemie International Edition, 2020
    Co-Authors: Gregory L. Challis, Matthew Jenner, Joleen Masschelein, Isolda Romero-canelón, Yousef Dashti, Ioanna T. Nakou, Eshwar Mahenthiralingam
    Abstract:

    A gene cluster encoding a cryptic trans -acyl transferase polyketide synthase (PKS) was identified in the genomes of Burkholderia gladioli BCC0238 and BCC1622, both isolated from the lungs of cystic fibrosis patients. Bioinfomatics analyses indicated the PKS assembles a novel member of the Glutarimide class of antibiotics, hitherto only isolated from Streptomyces species. Screening of a range of growth parameters enabled gladiostatin, the metabolic product of the PKS, to be identified. NMR spectroscopic analysis revealed that gladiostatin, which has promising activity against several human cancer cell lines and inhibits tumor cell migration, contains an unusual 2-acyl-4-hydroxy-3-methylbutenolide in addition to the Glutarimide pharmacophore. An AfsA-like domain at the C-terminus of the PKS was shown to catalyze condensation of 3-ketothioesters with dihydroxyacetone phosphate, indicating it plays a key role in polyketide chain release and butenolide formation.

  • genomics driven discovery of a novel Glutarimide antibiotic from burkholderia gladioli reveals an unusual polyketide synthase chain release mechanism
    Angewandte Chemie, 2020
    Co-Authors: Ioanna T. Nakou, Matthew Jenner, Joleen Masschelein, Yousef Dashti, Eshwar Mahenthiralingam, Gregory L. Challis, Isolda Romerocanelon
    Abstract:

    A gene cluster encoding a cryptic trans-acyl transferase polyketide synthase (PKS) was identified in the genomes of Burkholderia gladioli BCC0238 and BCC1622, both isolated from the lungs of cystic fibrosis patients. Bioinfomatics analyses indicated the PKS assembles a novel member of the Glutarimide class of antibiotics, hitherto only isolated from Streptomyces species. Screening of a range of growth parameters led to the identification of gladiostatin, the metabolic product of the PKS. NMR spectroscopic analysis revealed that gladiostatin, which has promising activity against several human cancer cell lines and inhibits tumor cell migration, contains an unusual 2-acyl-4-hydroxy-3-methylbutenolide in addition to the Glutarimide pharmacophore. An AfsA-like domain at the C-terminus of the PKS was shown to catalyze condensation of 3-ketothioesters with dihydroxyacetone phosphate, thus indicating it plays a key role in polyketide chain release and butenolide formation.