Synthetic Biology Driven Biosynthesis of Unnatural Tropolone Sesquiterpenoids.
biosynthesis
meroterpenoid
pathway engineering
ring contraction
tropolone
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
21 12 2020
21 12 2020
Historique:
received:
21
07
2020
pubmed:
16
9
2020
medline:
20
3
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32929811
doi: 10.1002/anie.202009914
pmc: PMC7814671
doi:
Substances chimiques
Sesquiterpenes
0
Tropolone
7L6DL16P1T
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23870-23878Informations de copyright
© 2020 Wiley-VCH GmbH.
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