Characterization of the nocardiopsin biosynthetic gene cluster reveals similarities to and differences from the rapamycin and FK-506 pathways.
Chembiochem
; 16(6): 990-7, 2015 Apr 13.
Article
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| MEDLINE
| ID: mdl-25755076
ABSTRACT
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.
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MEDLINE
Asunto principal:
Familia de Multigenes
/
Tacrolimus
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Sirolimus
Idioma:
En
Año:
2015
Tipo del documento:
Article