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Title 

Characterization of Gel16 as a cytochrome P450 in geldanamycin biosynthesis and in-silico analysis for endogenous electron transport system

Authors 

H RimalS C YuByeongsan LeeYoung-Soo HongT J Oh

Publisher 

The Korean Society for Applied Microbiology

Issue Date 

2019

Citation 

Journal of Microbiology and Biotechnology

Keywords 

Biosynthetic pathwaycytochrome P450electron transport systemgeldanamycinin-silico analysisredox partner

Abstract 

Geldanamycin and its derivatives, inhibitors of heat shock protein 90, are considered potent anticancer drugs, although their biosynthetic pathways have not yet been fully elucidated. The key step of conversion of 4,5-dihydrogeldanamycin to geldanamycin was expected to catalyze by a P450 monooxygenase, Gel16. The adequate bioconversions by cytochrome P450 mostly rely upon its interaction with redox partners. Several ferredoxin and ferredoxin reductases are available in the genome of certain organisms, but only a few suitable partners can operate in full efficiency. In this study, we have expressed cytochrome P450 gel16 in Escherichia coli and performed an in vitro assay using 4,5-dihydrogeldanamycin as a substrate. We demonstrated that the in silico method can be applicable for the efficient mining of convenient endogenous redox partners (9 ferredoxins and 6 ferredoxin reductases) against CYP Gel16 from Streptomyces hygroscopicus. The distances for ligand FDX4-FDR6 were found to be 9.384 ?. Similarly, the binding energy between Gel16-FDX4 and FDX4-FDR6 were -611.88 kcal/mol and -834.48 kcal/mol, respectively, suggesting the lowest distance and binding energy rather than other redox partners. These findings suggest that the best redox partners of Gel16 could be NADPH → FDR6 → FDX4 → Gel16.

URI 

https://doi.org/10.4014/jmb.1809.09008

ISSN 

1017-7825

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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