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Discovery and characterization of the tubercidin biosynthetic pathway from Streptomyces tubercidicus NBRC 13090.
- Source :
-
Microbial Cell Factories . 8/28/2018, Vol. 17 Issue 1, pN.PAG-N.PAG. 1p. 2 Diagrams, 1 Chart, 4 Graphs. - Publication Year :
- 2018
-
Abstract
- Background: Tubercidin (TBN), an adenosine analog with potent antimycobacteria and antitumor bioactivities, highlights an intriguing structure, in which a 7-deazapurine core is linked to the ribose moiety by an N-glycosidic bond. However, the molecular logic underlying the biosynthesis of this antibiotic has remained poorly understood. Results: Here, we report the discovery and characterization of the TBN biosynthetic pathway from Streptomyces tubercidicus NBRC 13090 via reconstitution of its production in a heterologous host. We demonstrated that TubE specifically utilizes phosphoribosylpyrophosphate and 7-carboxy-7-deazaguanine for the precise construction of the deazapurine nucleoside scaffold. Moreover, we provided biochemical evidence that TubD functions as an NADPH-dependent reductase, catalyzing irreversible reductive deamination. Finally, we verified that TubG acts as a Nudix hydrolase, preferring Co2+ for the maintenance of maximal activity, and is responsible for the tailoring hydrolysis step leading to TBN. Conclusions: These findings lay a foundation for the rational generation of TBN analogs through synthetic biology strategy, and also open the way for the target-directed search of TBN-related antibiotics. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MYCOBACTERIA
*ADENOSINES
*PHOSPHORYLATION
*ANTINEOPLASTIC agents
*DNA polymerases
Subjects
Details
- Language :
- English
- ISSN :
- 14752859
- Volume :
- 17
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Microbial Cell Factories
- Publication Type :
- Academic Journal
- Accession number :
- 131488150
- Full Text :
- https://doi.org/10.1186/s12934-018-0978-8