Catalytic Control of Spiroketal Formation in Rubromycin Polyketide Biosynthesis.
antibiotics
collinone
lenticulone
polyketide synthase
redox tailoring
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:
20 12 2021
20 12 2021
Historique:
revised:
07
10
2021
received:
19
07
2021
pubmed:
16
10
2021
medline:
13
1
2022
entrez:
15
10
2021
Statut:
ppublish
Résumé
The medically important bacterial aromatic polyketide natural products typically feature a planar, polycyclic core structure. An exception is found for the rubromycins, whose backbones are disrupted by a bisbenzannulated [5,6]-spiroketal pharmacophore that was recently shown to be assembled by flavin-dependent enzymes. In particular, a flavoprotein monooxygenase proved critical for the drastic oxidative rearrangement of a pentangular precursor and the installment of an intermediate [6,6]-spiroketal moiety. Here we provide structural and mechanistic insights into the control of catalysis by this spiroketal synthase, which fulfills several important functions as reductase, monooxygenase, and presumably oxidase. The enzyme hereby tightly controls the redox state of the substrate to counteract shunt product formation, while also steering the cleavage of three carbon-carbon bonds. Our work illustrates an exceptional strategy for the biosynthesis of stable chroman spiroketals.
Identifiants
pubmed: 34652045
doi: 10.1002/anie.202109384
pmc: PMC9299503
doi:
Substances chimiques
Ethers
0
Quinones
0
Flavin-Adenine Dinucleotide
146-14-5
NADP
53-59-8
Mixed Function Oxygenases
EC 1.-
Quinone Reductases
EC 1.6.99.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
26960-26970Subventions
Organisme : Austrian Science Fund FWF
ID : J 4482
Pays : Austria
Organisme : austrian science fund
ID : J 4482-B
Organisme : deutsche forschungsgemeinschaft
ID : TE 931/4-1
Organisme : deutsche forschungsgemeinschaft
ID : TE 931/3-1
Informations de copyright
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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