Details
| Translated title of the contribution | Heterologe Produktion pilzlicher Maleidride enthüllt die kryptische Cyclisierung in ihrer Biosynthese |
|---|---|
| Original language | English |
| Pages (from-to) | 6784-6788 |
| Number of pages | 5 |
| Journal | Angewandte Chemie |
| Volume | 55 |
| Issue number | 23 |
| Early online date | 21 Apr 2016 |
| Publication status | Published - 27 May 2016 |
Abstract
Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins. Ring cycle: The enzymes involved in the cyclization of the maleidride family of bioactive fungal natural products, including agnestadride A and byssochlamic acid, were identified. These previously unknown proteins show homology to ketosteroid isomerases (KI-like) and phosphatidylethanolamine-binding proteins (PEBP-like).
Keywords
- biosynthesis, cyclization, enzymes, maleidride, polyketides
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
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In: Angewandte Chemie , Vol. 55, No. 23, 27.05.2016, p. 6784-6788.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
AU - Williams, Katherine
AU - Szwalbe, Agnieszka J.
AU - Mulholland, Nicholas P.
AU - Vincent, Jason L.
AU - Bailey, Andrew M.
AU - Willis, Christine L.
AU - Simpson, Thomas J.
AU - Cox, Russell J.
N1 - Funding information: We thank BBSRC (KW, BB/J006289/1) and Syngenta (AS) for funding. Analytical and preparative LCMS were provide by EPSRC (EP/F066104/1) and DFG (INST 187/621). 500 MHz NMR (EP/L011999/1) was provided by EPSRC. We thank Dr Kate de Mattos-Shipley (BB/K002341/1) for helpful discussions and bioinformatic assistance with maleidride clusters.
PY - 2016/5/27
Y1 - 2016/5/27
N2 - Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins. Ring cycle: The enzymes involved in the cyclization of the maleidride family of bioactive fungal natural products, including agnestadride A and byssochlamic acid, were identified. These previously unknown proteins show homology to ketosteroid isomerases (KI-like) and phosphatidylethanolamine-binding proteins (PEBP-like).
AB - Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins. Ring cycle: The enzymes involved in the cyclization of the maleidride family of bioactive fungal natural products, including agnestadride A and byssochlamic acid, were identified. These previously unknown proteins show homology to ketosteroid isomerases (KI-like) and phosphatidylethanolamine-binding proteins (PEBP-like).
KW - biosynthesis
KW - cyclization
KW - enzymes
KW - maleidride
KW - polyketides
UR - http://www.scopus.com/inward/record.url?scp=84971330701&partnerID=8YFLogxK
U2 - 10.1002/anie.201511882
DO - 10.1002/anie.201511882
M3 - Article
C2 - 27099957
AN - SCOPUS:84971330701
VL - 55
SP - 6784
EP - 6788
JO - Angewandte Chemie
JF - Angewandte Chemie
SN - 1433-7851
IS - 23
ER -