Details
| Translated title of the contribution | Synthetisch biologisch getriebene Biosynthese von unnatürlichen Tropolon‐Sesquiterpenoiden |
|---|---|
| Original language | English |
| Pages (from-to) | 23870-23878 |
| Number of pages | 9 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 59 |
| Issue number | 52 |
| Early online date | 15 Sept 2020 |
| Publication status | Published - 14 Dec 2020 |
Abstract
Tropolone sesquiterpenoids (TS) are an intriguing family of biologically active fungal meroterpenoids that arise through a unique intermolecular hetero Diels–Alder (hDA) reaction between humulene and tropolones. Here, we report on the combinatorial biosynthesis of a series of unprecedented analogs of the TS pycnidione 1 and xenovulene A 2. In a systematic synthetic biology driven approach, we recombined genes from three TS biosynthetic gene clusters (pycnidione 1, xenovulene A 2 and eupenifeldin 3) in the fungal host Aspergillus oryzae NSAR1. Rational design of the reconstituted pathways granted control over the number of hDA reactions taking place, the chemical nature of the fused polyketide moiety (tropolono- vs. monobenzo-pyranyl) and the degree of hydroxylation. Formation of unexpected monobenzopyranyl sesquiterpenoids was investigated using isotope-feeding studies to reveal a new and highly unusual oxidative ring contraction rearrangement.
Keywords
- biosynthesis, meroterpenoid, pathway engineering, ring contraction, tropolone
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
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In: Angewandte Chemie - International Edition, Vol. 59, No. 52, 14.12.2020, p. 23870-23878.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Synthetic Biology Driven Biosynthesis of Unnatural Tropolone Sesquiterpenoids
AU - Schotte, Carsten
AU - Li, Lei
AU - Wibberg, Daniel
AU - Kalinowski, Jörn
AU - Cox, Russell J.
N1 - Funding Information: CS thanks Leibniz University for funding. LL thanks the Chinese Scholarship Council for funding (CSC 201704910820). Fundación MEDINA (Olga Genilloud/Víctor González Menéndez) are thanked for strains and culturing conditions. Jörg Fohrer and Luca Codutti are thanked for assisting with 2D‐nOe data. DFG is thanked for the provision of NMR and LCMS equipment (INST 187/621‐1, INST 187/686‐1). Open access funding enabled and organized by Projekt DEAL.
PY - 2020/12/14
Y1 - 2020/12/14
N2 - Tropolone sesquiterpenoids (TS) are an intriguing family of biologically active fungal meroterpenoids that arise through a unique intermolecular hetero Diels–Alder (hDA) reaction between humulene and tropolones. Here, we report on the combinatorial biosynthesis of a series of unprecedented analogs of the TS pycnidione 1 and xenovulene A 2. In a systematic synthetic biology driven approach, we recombined genes from three TS biosynthetic gene clusters (pycnidione 1, xenovulene A 2 and eupenifeldin 3) in the fungal host Aspergillus oryzae NSAR1. Rational design of the reconstituted pathways granted control over the number of hDA reactions taking place, the chemical nature of the fused polyketide moiety (tropolono- vs. monobenzo-pyranyl) and the degree of hydroxylation. Formation of unexpected monobenzopyranyl sesquiterpenoids was investigated using isotope-feeding studies to reveal a new and highly unusual oxidative ring contraction rearrangement.
AB - Tropolone sesquiterpenoids (TS) are an intriguing family of biologically active fungal meroterpenoids that arise through a unique intermolecular hetero Diels–Alder (hDA) reaction between humulene and tropolones. Here, we report on the combinatorial biosynthesis of a series of unprecedented analogs of the TS pycnidione 1 and xenovulene A 2. In a systematic synthetic biology driven approach, we recombined genes from three TS biosynthetic gene clusters (pycnidione 1, xenovulene A 2 and eupenifeldin 3) in the fungal host Aspergillus oryzae NSAR1. Rational design of the reconstituted pathways granted control over the number of hDA reactions taking place, the chemical nature of the fused polyketide moiety (tropolono- vs. monobenzo-pyranyl) and the degree of hydroxylation. Formation of unexpected monobenzopyranyl sesquiterpenoids was investigated using isotope-feeding studies to reveal a new and highly unusual oxidative ring contraction rearrangement.
KW - biosynthesis
KW - meroterpenoid
KW - pathway engineering
KW - ring contraction
KW - tropolone
UR - http://www.scopus.com/inward/record.url?scp=85093698328&partnerID=8YFLogxK
U2 - 10.1002/anie.202009914
DO - 10.1002/anie.202009914
M3 - Article
VL - 59
SP - 23870
EP - 23878
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 52
ER -