Details
| Original language | English |
|---|---|
| Pages (from-to) | 8756-8760 |
| Number of pages | 5 |
| Journal | Organic letters |
| Volume | 21 |
| Issue number | 21 |
| Early online date | 23 Oct 2019 |
| Publication status | Published - 1 Nov 2019 |
Abstract
Tailoring enzymes in cytochalasan biosynthesis are relatively promiscuous. Exploiting this property, we deduced the function of four cryptic cytochrome P450 monooxygenases via heterologous expression of six cytochrome P450-encoding genes, originating from Hypoxylon fragiforme and Pyricularia oryzae, in pyrichalasin H ΔP450 strains. Three cryptic cytochrome P450 enzymes (HffD, HffG, and CYP1) restored pyrichalasin H production in mutant strains, while CYP3 catalyzed a site-selective epoxidation leading to the isolation of three novel cytochalasans.
Keywords
- Biocatalysis, Cytochrome P-450 Enzyme System/genetics, Enzyme Assays/methods, Mutation, Xylariales/enzymology
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Chemistry(all)
- Physical and Theoretical Chemistry
- Chemistry(all)
- Organic Chemistry
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In: Organic letters, Vol. 21, No. 21, 01.11.2019, p. 8756-8760.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Investigating the Function of Cryptic Cytochalasan Cytochrome P450 Monooxygenases Using Combinatorial Biosynthesis
AU - Wang, Chongqing
AU - Becker, Kevin
AU - Pfütze, Sebastian
AU - Kuhnert, Eric
AU - Stadler, Marc
AU - Cox, Russell John
AU - Skellam, Elizabeth Julia
N1 - Funding information: This work benefitted from the sharing of expertise within the DFG priority program SPP 1991 Taxon-Omics and support from DFG [Grant Nos. CO 1328/4-1, CO 1328/2-1, INST 187/621-1, INST 187/686-1)]. This work was also supported by the Chinese Scholarship Council [Chongqing Wang (201608310143)]. We thank Dr. Boyke Bunk and Dr. Cathrin Spröer (DSMZ, Braunschweig) for PacBio sequencing of H. fragiforme MUCL 51264 and Dr. Daniel Wibberg and Professor Jörn Kalinowski (CeBiTec, Bielefeld) for annotation of the H. fragiforme genome. We also thank Leibniz University Hannover students Teresa Tamara and Michelle Angelica Djuari for assistance with extracting fungal cultures and preparing gDNA.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Tailoring enzymes in cytochalasan biosynthesis are relatively promiscuous. Exploiting this property, we deduced the function of four cryptic cytochrome P450 monooxygenases via heterologous expression of six cytochrome P450-encoding genes, originating from Hypoxylon fragiforme and Pyricularia oryzae, in pyrichalasin H ΔP450 strains. Three cryptic cytochrome P450 enzymes (HffD, HffG, and CYP1) restored pyrichalasin H production in mutant strains, while CYP3 catalyzed a site-selective epoxidation leading to the isolation of three novel cytochalasans.
AB - Tailoring enzymes in cytochalasan biosynthesis are relatively promiscuous. Exploiting this property, we deduced the function of four cryptic cytochrome P450 monooxygenases via heterologous expression of six cytochrome P450-encoding genes, originating from Hypoxylon fragiforme and Pyricularia oryzae, in pyrichalasin H ΔP450 strains. Three cryptic cytochrome P450 enzymes (HffD, HffG, and CYP1) restored pyrichalasin H production in mutant strains, while CYP3 catalyzed a site-selective epoxidation leading to the isolation of three novel cytochalasans.
KW - Biocatalysis
KW - Cytochrome P-450 Enzyme System/genetics
KW - Enzyme Assays/methods
KW - Mutation
KW - Xylariales/enzymology
UR - http://www.scopus.com/inward/record.url?scp=85074380089&partnerID=8YFLogxK
U2 - 10.1021/acs.orglett.9b03372
DO - 10.1021/acs.orglett.9b03372
M3 - Article
C2 - 31644300
AN - SCOPUS:85074380089
VL - 21
SP - 8756
EP - 8760
JO - Organic letters
JF - Organic letters
SN - 1523-7060
IS - 21
ER -