Details
| Original language | English |
|---|---|
| Pages (from-to) | 1727-1730 |
| Number of pages | 4 |
| Journal | Chemical communications |
| Volume | 53 |
| Issue number | 10 |
| Publication status | Published - 1 Jan 2017 |
Abstract
Six potential diketide substrates for the squalestatin tetraketide synthase (SQTKS) dehydratase (DH) domain were synthesised as N-acetyl cysteamine thiolesters (SNAC) and tested in kinetic assays as substrates with an isolated DH domain. 3R-3-hydroxybutyryl SNAC 3R-16 was turned over by the enzyme, but its enantiomer was not. Of the four 2-methyl substrates only 2R,3R-2-methyl-3-hydroxybutyryl SNAC 2R,3R-8 was a substrate. Combined with stereochemical information from the isolated SQTKS enoyl reductase (ER) domain, our results provide a near complete stereochemical description of the first cycle of beta-modification reactions of a fungal highly reducing polyketide synthase (HR-PKS). The results emphasise the close relationship between fungal HR-PKS and vertebrate fatty acid synthases (vFAS).
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Materials Science(all)
- Electronic, Optical and Magnetic Materials
- Materials Science(all)
- Ceramics and Composites
- Chemistry(all)
- Materials Science(all)
- Surfaces, Coatings and Films
- Materials Science(all)
- Metals and Alloys
- Materials Science(all)
- Materials Chemistry
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In: Chemical communications, Vol. 53, No. 10, 01.01.2017, p. 1727-1730.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase
AU - Liddle, Emma
AU - Scott, Alan
AU - Han, Li Chen
AU - Ivison, David
AU - Simpson, Thomas J.
AU - Willis, Christine L.
AU - Cox, Russell J.
N1 - Funding information: We thank EPSRC (EP/F066104/1) for LCMS equipment, BBSRC (BB/I003355/1) for funding AS and BrisSynBio Synthetic Biology Research Centre, (BB/L01386X/1) for funding L-CH. E. L. and D. I. were funded by the School of Chemistry, University of Bristol. We thank Dr J. E. Nettleship at the Oxford Protein Production Facility (OPPF) for assistance with protein production. Hao Yao and Oliver Piech (LUH) are thanked for technical assistance.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Six potential diketide substrates for the squalestatin tetraketide synthase (SQTKS) dehydratase (DH) domain were synthesised as N-acetyl cysteamine thiolesters (SNAC) and tested in kinetic assays as substrates with an isolated DH domain. 3R-3-hydroxybutyryl SNAC 3R-16 was turned over by the enzyme, but its enantiomer was not. Of the four 2-methyl substrates only 2R,3R-2-methyl-3-hydroxybutyryl SNAC 2R,3R-8 was a substrate. Combined with stereochemical information from the isolated SQTKS enoyl reductase (ER) domain, our results provide a near complete stereochemical description of the first cycle of beta-modification reactions of a fungal highly reducing polyketide synthase (HR-PKS). The results emphasise the close relationship between fungal HR-PKS and vertebrate fatty acid synthases (vFAS).
AB - Six potential diketide substrates for the squalestatin tetraketide synthase (SQTKS) dehydratase (DH) domain were synthesised as N-acetyl cysteamine thiolesters (SNAC) and tested in kinetic assays as substrates with an isolated DH domain. 3R-3-hydroxybutyryl SNAC 3R-16 was turned over by the enzyme, but its enantiomer was not. Of the four 2-methyl substrates only 2R,3R-2-methyl-3-hydroxybutyryl SNAC 2R,3R-8 was a substrate. Combined with stereochemical information from the isolated SQTKS enoyl reductase (ER) domain, our results provide a near complete stereochemical description of the first cycle of beta-modification reactions of a fungal highly reducing polyketide synthase (HR-PKS). The results emphasise the close relationship between fungal HR-PKS and vertebrate fatty acid synthases (vFAS).
UR - http://www.scopus.com/inward/record.url?scp=85011103494&partnerID=8YFLogxK
U2 - 10.1039/c6cc10172k
DO - 10.1039/c6cc10172k
M3 - Article
C2 - 28106181
AN - SCOPUS:85011103494
VL - 53
SP - 1727
EP - 1730
JO - Chemical communications
JF - Chemical communications
SN - 1359-7345
IS - 10
ER -