sirolimus has been researched along with tetrahydrofuran* in 1 studies
1 other study(ies) available for sirolimus and tetrahydrofuran
| Article | Year |
|---|---|
Characterization of the nocardiopsin biosynthetic gene cluster reveals similarities to and differences from the rapamycin and FK-506 pathways.
Macrolide-pipecolate natural products, such as rapamycin (1) and FK-506 (2), are renowned modulators of FK506-binding proteins (FKBPs). The nocardiopsins, from Nocardiopsis sp. CMB-M0232, are the newest members of this structural class. Here, the biosynthetic pathway for nocardiopsins A-D (4-7) is revealed by cloning, sequencing, and bioinformatic analyses of the nsn gene cluster. In vitro evaluation of recombinant NsnL revealed that this lysine cyclodeaminase catalyzes the conversion of L-lysine into the L-pipecolic acid incorporated into 4 and 5. Bioinformatic analyses supported the conjecture that a linear nocardiopsin precursor is equipped with the hydroxy group required for macrolide closure in a previously unobserved manner by employing a P450 epoxidase (NsnF) and limonene epoxide hydrolase homologue (NsnG). The nsn cluster also encodes candidates for tetrahydrofuran group biosynthesis. The nocardiopsin pathway provides opportunities for engineering of FKBP-binding metabolites and for probing new enzymology in nature's polyketide tailoring arsenal. Topics: Actinomycetales; Amino Acid Sequence; Ammonia-Lyases; Biocatalysis; Cloning, Molecular; Computational Biology; Furans; Molecular Sequence Data; Multigene Family; Pipecolic Acids; Sirolimus; Tacrolimus | 2015 |