Details
| Original language | English |
|---|---|
| Pages (from-to) | 11895-11903 |
| Number of pages | 9 |
| Journal | Chemistry – A European Journal |
| Volume | 27 |
| Issue number | 46 |
| Early online date | 11 Jun 2021 |
| Publication status | Published - 16 Aug 2021 |
Abstract
The mycotoxin terrein is derived from the C 10-precursor 6-hydroxymellein (6-HM) via an oxidative ring contraction. Although the corresponding biosynthetic gene cluster (BGC) has been identified, details of the enzymatic oxidative transformations are lacking. Combining heterologous expression and in vitro studies we show that the flavin-dependent monooxygenase (FMO) TerC catalyzes the initial oxidative decarboxylation of 6-HM. The reactive intermediate is further hydroxylated by the second FMO TerD to yield a highly oxygenated aromatic species, but further reconstitution of the pathway was hampered. A related BGC was identified in the marine-derived Roussoella sp. DLM33 and confirmed by heterologous expression. These studies demonstrate that the biosynthetic pathways of terrein and related (polychlorinated) congeners diverge after oxidative decarboxylation of the lactone precursor that is catalyzed by a conserved FMO and further indicate that early dehydration of the side chain is an essential step.
Keywords
- 6-hydroxymellein, cryptosporiopsin, flavin-dependent monooxygenase, oxidative decarboxylation, terrein
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
Sustainable Development Goals
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Chemistry – A European Journal, Vol. 27, No. 46, 16.08.2021, p. 11895-11903.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Early Oxidative Transformations During the Biosynthesis of Terrein and Related Natural Products
AU - Kahlert, Lukas
AU - Bernardi, Darlon
AU - Hauser, Maurice
AU - Ióca, Laura P.
AU - Berlinck, Roberto G. S.
AU - Skellam, Elizabeth J.
AU - Cox, Russell J.
N1 - Funding Information: Matthias Brock is thanked for the gift of Aspergillus terreus SBUG844. LK was funded by DFG (CO 1328/5-1). MH is funded by DFG (CO 1328 / 9?1). DFG is thanked for the provision of LCMS (DFG, INST 187/621-1,) and NMR (INST 187/686-1) instrumentation. RGSB, DIB and LPI were funded by FAPESP (2013/50228-8, 2019/17721-9, 2016/21341-9, 2020/11691-8, 2018/10742-8, 2016/05133-7). Open access funding enabled and organized by Projekt DEAL. Funding Information: Matthias Brock is thanked for the gift of SBUG844. LK was funded by DFG (CO 1328/5‐1). MH is funded by DFG (CO 1328 / 9–1). DFG is thanked for the provision of LCMS (DFG, INST 187/621‐1,) and NMR (INST 187/686‐1) instrumentation. RGSB, DIB and LPI were funded by FAPESP (2013/50228‐8, 2019/17721‐9, 2016/21341‐9, 2020/11691‐8, 2018/10742‐8, 2016/05133‐7). Open access funding enabled and organized by Projekt DEAL. Aspergillus terreus
PY - 2021/8/16
Y1 - 2021/8/16
N2 - The mycotoxin terrein is derived from the C 10-precursor 6-hydroxymellein (6-HM) via an oxidative ring contraction. Although the corresponding biosynthetic gene cluster (BGC) has been identified, details of the enzymatic oxidative transformations are lacking. Combining heterologous expression and in vitro studies we show that the flavin-dependent monooxygenase (FMO) TerC catalyzes the initial oxidative decarboxylation of 6-HM. The reactive intermediate is further hydroxylated by the second FMO TerD to yield a highly oxygenated aromatic species, but further reconstitution of the pathway was hampered. A related BGC was identified in the marine-derived Roussoella sp. DLM33 and confirmed by heterologous expression. These studies demonstrate that the biosynthetic pathways of terrein and related (polychlorinated) congeners diverge after oxidative decarboxylation of the lactone precursor that is catalyzed by a conserved FMO and further indicate that early dehydration of the side chain is an essential step.
AB - The mycotoxin terrein is derived from the C 10-precursor 6-hydroxymellein (6-HM) via an oxidative ring contraction. Although the corresponding biosynthetic gene cluster (BGC) has been identified, details of the enzymatic oxidative transformations are lacking. Combining heterologous expression and in vitro studies we show that the flavin-dependent monooxygenase (FMO) TerC catalyzes the initial oxidative decarboxylation of 6-HM. The reactive intermediate is further hydroxylated by the second FMO TerD to yield a highly oxygenated aromatic species, but further reconstitution of the pathway was hampered. A related BGC was identified in the marine-derived Roussoella sp. DLM33 and confirmed by heterologous expression. These studies demonstrate that the biosynthetic pathways of terrein and related (polychlorinated) congeners diverge after oxidative decarboxylation of the lactone precursor that is catalyzed by a conserved FMO and further indicate that early dehydration of the side chain is an essential step.
KW - 6-hydroxymellein
KW - cryptosporiopsin
KW - flavin-dependent monooxygenase
KW - oxidative decarboxylation
KW - terrein
UR - http://www.scopus.com/inward/record.url?scp=85108360649&partnerID=8YFLogxK
U2 - 10.1002/chem.202101447
DO - 10.1002/chem.202101447
M3 - Article
VL - 27
SP - 11895
EP - 11903
JO - Chemistry – A European Journal
JF - Chemistry – A European Journal
SN - 1521-3765
IS - 46
ER -