Details
| Original language | English |
|---|---|
| Pages (from-to) | 2930-2939 |
| Number of pages | 10 |
| Journal | Chemical science |
| Volume | 10 |
| Issue number | 10 |
| Publication status | Published - 14 Mar 2019 |
| Externally published | Yes |
Abstract
Three novel dimeric xanthones, cryptosporioptides A-C were isolated from Cryptosporiopsis sp. 8999 and their structures elucidated. Methylation of cryptosporioptide A gave a methyl ester with identical NMR data to cryptosporioptide, a compound previously reported to have been isolated from the same fungus. However, HRMS analysis revealed that cryptosporioptide is a symmetrical dimer, not a monomer as previously proposed, and the revised structure was elucidated by extensive NMR analysis. The genome of Cryptosporiopsis sp. 8999 was sequenced and the dimeric xanthone (dmx) biosynthetic gene cluster responsible for the production of the cryptosporioptides was identified. Gene disruption experiments identified a gene (dmxR5) encoding a cytochrome P450 oxygenase as being responsible for the dimerisation step late in the biosynthetic pathway. Disruption of dmxR5 led to the isolation of novel monomeric xanthones. Cryptosporioptide B and C feature an unusual ethylmalonate subunit: a hrPKS and acyl CoA carboxylase are responsible for its formation. Bioinformatic analysis of the genomes of several fungi producing related xanthones, e.g. the widely occurring ergochromes, and related metabolites allows detailed annotation of the biosynthetic genes, and a rational overall biosynthetic scheme for the production of fungal dimeric xanthones to be proposed.
ASJC Scopus subject areas
- Chemistry(all)
- General Chemistry
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In: Chemical science, Vol. 10, No. 10, 14.03.2019, p. 2930-2939.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Structure revision of cryptosporioptides and determination of the genetic basis for dimeric xanthone biosynthesis in fungi
AU - Greco, Claudio
AU - De Mattos-Shipley, Kate
AU - Bailey, Andrew M.
AU - Mulholland, Nicholas P.
AU - Vincent, Jason L.
AU - Willis, Christine L.
AU - Cox, Russell J.
AU - Simpson, Thomas J.
N1 - Funding information: We thank BBSRC (BB/J006289/1, BB/L01386X/1) and Syngenta for funding. LCMS instruments were provided by EPSRC (EP/ F066104/1) and DFG (INST 187/621). 500 MHz NMR (EP/ L011999/1) was provided by EPSRC. Cryptosporiopsis sp. 8999 was a kind gi? from Dr Barbara Schulz and its genome was sequenced at the University of Cambridge Sequencing Centre. Markiyan Samborskyy is thanked for assistance with bio-informatics. Katherine Williams and Zhongshu Song are thanked for technical assistance.
PY - 2019/3/14
Y1 - 2019/3/14
N2 - Three novel dimeric xanthones, cryptosporioptides A-C were isolated from Cryptosporiopsis sp. 8999 and their structures elucidated. Methylation of cryptosporioptide A gave a methyl ester with identical NMR data to cryptosporioptide, a compound previously reported to have been isolated from the same fungus. However, HRMS analysis revealed that cryptosporioptide is a symmetrical dimer, not a monomer as previously proposed, and the revised structure was elucidated by extensive NMR analysis. The genome of Cryptosporiopsis sp. 8999 was sequenced and the dimeric xanthone (dmx) biosynthetic gene cluster responsible for the production of the cryptosporioptides was identified. Gene disruption experiments identified a gene (dmxR5) encoding a cytochrome P450 oxygenase as being responsible for the dimerisation step late in the biosynthetic pathway. Disruption of dmxR5 led to the isolation of novel monomeric xanthones. Cryptosporioptide B and C feature an unusual ethylmalonate subunit: a hrPKS and acyl CoA carboxylase are responsible for its formation. Bioinformatic analysis of the genomes of several fungi producing related xanthones, e.g. the widely occurring ergochromes, and related metabolites allows detailed annotation of the biosynthetic genes, and a rational overall biosynthetic scheme for the production of fungal dimeric xanthones to be proposed.
AB - Three novel dimeric xanthones, cryptosporioptides A-C were isolated from Cryptosporiopsis sp. 8999 and their structures elucidated. Methylation of cryptosporioptide A gave a methyl ester with identical NMR data to cryptosporioptide, a compound previously reported to have been isolated from the same fungus. However, HRMS analysis revealed that cryptosporioptide is a symmetrical dimer, not a monomer as previously proposed, and the revised structure was elucidated by extensive NMR analysis. The genome of Cryptosporiopsis sp. 8999 was sequenced and the dimeric xanthone (dmx) biosynthetic gene cluster responsible for the production of the cryptosporioptides was identified. Gene disruption experiments identified a gene (dmxR5) encoding a cytochrome P450 oxygenase as being responsible for the dimerisation step late in the biosynthetic pathway. Disruption of dmxR5 led to the isolation of novel monomeric xanthones. Cryptosporioptide B and C feature an unusual ethylmalonate subunit: a hrPKS and acyl CoA carboxylase are responsible for its formation. Bioinformatic analysis of the genomes of several fungi producing related xanthones, e.g. the widely occurring ergochromes, and related metabolites allows detailed annotation of the biosynthetic genes, and a rational overall biosynthetic scheme for the production of fungal dimeric xanthones to be proposed.
UR - http://www.scopus.com/inward/record.url?scp=85062593645&partnerID=8YFLogxK
U2 - 10.1039/c8sc05126g
DO - 10.1039/c8sc05126g
M3 - Article
C2 - 30996871
AN - SCOPUS:85062593645
VL - 10
SP - 2930
EP - 2939
JO - Chemical science
JF - Chemical science
SN - 2041-6520
IS - 10
ER -