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Cyanobacterial ent ‐Sterol‐Like Natural Products from a Deviated Ubiquinone Pathway
Author(s) -
Moosmann Philipp,
Ueoka Reiko,
Grauso Laura,
Mangoni Alfonso,
Morinaka Brandon I.,
Gugger Muriel,
Piel Jörn
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201611617
Subject(s) - sterol , genome , biology , moiety , terpene , computational biology , drug discovery , natural product , biochemistry , gene , chemistry , stereochemistry , cholesterol
Natural products from marine animals show high potential for the development of new medicines, but drug development based on these compounds is commonly hampered by their low natural abundance. Since many of these metabolites are suspected or known to be produced by uncultivated bacterial symbionts, the rapidly growing diversity of sequenced prokaryotic genomes offers the opportunity to identify alternative, culturable sources of natural products computationally. In this work, we investigated the potential of using this sequenced resource to facilitate the production of meroterpenoid‐like compounds related to those from marine sources. This genome‐mining strategy revealed a biosynthetic gene cluster for highly modified cytotoxic meroterpenoids related to pelorol and other compounds isolated from sponges. Functional characterization of the terpene cyclase MstE showed that it generates an ent‐sterol‐like skeleton fused to an aryl moiety from an open‐chain precursor and is therefore a promising tool for the chemoenzymatic preparation of synthetically challenging chemical scaffolds.