Nahuoic acid A produced by a Streptomyces sp. isolated from a marine sediment is a selective SAM-competitive inhibitor of the histone methyltransferase SETD8

David E Williams; Doralyn S Dalisay; Fengling Li; James Amphlett; Wisanu Maneerat; Miguel Angel Garcia Chavez; Yan Alexander Wang; Teatulohi Matainaho; Wenyu Yu; Peter J Brown; Cheryl H Arrowsmith; Masoud Vedadi; Raymond J Andersen

doi:10.1021/ol303416k

Nahuoic acid A produced by a Streptomyces sp. isolated from a marine sediment is a selective SAM-competitive inhibitor of the histone methyltransferase SETD8

Org Lett. 2013 Jan 18;15(2):414-7. doi: 10.1021/ol303416k. Epub 2012 Dec 28.

Authors

David E Williams¹, Doralyn S Dalisay, Fengling Li, James Amphlett, Wisanu Maneerat, Miguel Angel Garcia Chavez, Yan Alexander Wang, Teatulohi Matainaho, Wenyu Yu, Peter J Brown, Cheryl H Arrowsmith, Masoud Vedadi, Raymond J Andersen

Affiliation

¹ Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.

PMID: 23272941
DOI: 10.1021/ol303416k

Abstract

The histone lysine monomethyltransferase SETD8 is an epigenetic regulator of cell cycle progression. Nahuoic acid A (1), a polyketide produced in culture by a Streptomyces sp. obtained from a tropical marine sediment, is the first known selective SAM-competitive inhibitor of SETD8. The structure of nahuoic acid A (1) has been elucidated by chemical transformation and detailed analysis of spectroscopic data.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Geologic Sediments / chemistry*
Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Polyketides / chemistry
Polyketides / isolation & purification*
Polyketides / pharmacology*
Streptomyces / chemistry*

Substances

Polyketides
nahuoic acid A
Histone-Lysine N-Methyltransferase