Details
| Original language | English |
|---|---|
| Pages (from-to) | 1227-1231 |
| Number of pages | 5 |
| Journal | Chemical science |
| Volume | 10 |
| Issue number | 4 |
| Early online date | 15 Nov 2018 |
| Publication status | Published - 28 Jan 2019 |
Abstract
The squalestatins are a class of highly complex fungal metabolites which are potent inhibitors of squalene synthase with potential use in the control of cholesterol biosynthesis. Little is known of the chemical steps involved in the construction of the 4,8-dioxa-bicyclo[3.2.1]octane core. Here, using a combination of directed gene knockout and heterologous expression experiments, we show that two putative non-heme-iron-dependent enzymes appear to catalyse a remarkable series of six consecutive oxidations which set up the bioactive core of the squalestatins. This is followed by the action of an unusual copper-dependent oxygenase which introduces a hydroxyl required for later acetylation.
ASJC Scopus subject areas
- Chemistry(all)
- General Chemistry
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In: Chemical science, Vol. 10, No. 4, 28.01.2019, p. 1227-1231.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Oxidative steps during the biosynthesis of squalestatin S1
AU - Lebe, Karen E.
AU - Cox, Russell J.
N1 - Funding information: KEL thanks the Leibniz Universität Hannover for funding. DFG is thanked for the provision of LCMS equipment (INST 187/621-1). Simon Blazy, Annika Stein and Michelangelo Marasco are thanked for technical assistance. Dr Gerald Dräger is thanked for assistance with HRMS and MSMS.
PY - 2019/1/28
Y1 - 2019/1/28
N2 - The squalestatins are a class of highly complex fungal metabolites which are potent inhibitors of squalene synthase with potential use in the control of cholesterol biosynthesis. Little is known of the chemical steps involved in the construction of the 4,8-dioxa-bicyclo[3.2.1]octane core. Here, using a combination of directed gene knockout and heterologous expression experiments, we show that two putative non-heme-iron-dependent enzymes appear to catalyse a remarkable series of six consecutive oxidations which set up the bioactive core of the squalestatins. This is followed by the action of an unusual copper-dependent oxygenase which introduces a hydroxyl required for later acetylation.
AB - The squalestatins are a class of highly complex fungal metabolites which are potent inhibitors of squalene synthase with potential use in the control of cholesterol biosynthesis. Little is known of the chemical steps involved in the construction of the 4,8-dioxa-bicyclo[3.2.1]octane core. Here, using a combination of directed gene knockout and heterologous expression experiments, we show that two putative non-heme-iron-dependent enzymes appear to catalyse a remarkable series of six consecutive oxidations which set up the bioactive core of the squalestatins. This is followed by the action of an unusual copper-dependent oxygenase which introduces a hydroxyl required for later acetylation.
UR - http://www.scopus.com/inward/record.url?scp=85060678685&partnerID=8YFLogxK
U2 - 10.1039/c8sc02615g
DO - 10.1039/c8sc02615g
M3 - Article
AN - SCOPUS:85060678685
VL - 10
SP - 1227
EP - 1231
JO - Chemical science
JF - Chemical science
SN - 2041-6520
IS - 4
ER -