Structural Basis of Cyclic 1,3-Diene Forming Acyl-Coenzyme A Dehydrogenases.
acyl-CoA dehydrogenases
enzyme catalysis
fatty acid oxidation
flavins
oxidoreductases
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
16 11 2021
16 11 2021
Historique:
revised:
15
09
2021
received:
16
08
2021
pubmed:
24
9
2021
medline:
22
2
2022
entrez:
23
9
2021
Statut:
ppublish
Résumé
The biologically important, FAD-containing acyl-coenzyme A (CoA) dehydrogenases (ACAD) usually catalyze the anti-1,2-elimination of a proton and a hydride of aliphatic CoA thioesters. Here, we report on the structure and function of an ACAD from anaerobic bacteria catalyzing the unprecedented 1,4-elimination at C3 and C6 of cyclohex-1-ene-1-carboxyl-CoA (Ch1CoA) to cyclohex-1,5-diene-1-carboxyl-CoA (Ch1,5CoA) and at C3 and C4 of the latter to benzoyl-CoA. Based on high-resolution Ch1CoA dehydrogenase crystal structures, the unorthodox reactivity is explained by the presence of a catalytic aspartate base (D91) at C3, and by eliminating the catalytic glutamate base at C1. Moreover, C6 of Ch1CoA and C4 of Ch1,5CoA are positioned towards FAD-N5 to favor the biologically relevant C3,C6- over the C3,C4-dehydrogenation activity. The C1,C2-dehydrogenation activity was regained by structure-inspired amino acid exchanges. The results provide the structural rationale for the extended catalytic repertoire of ACADs and offer previously unknown biocatalytic options for the synthesis of cyclic 1,3-diene building blocks.
Identifiants
pubmed: 34555236
doi: 10.1002/cbic.202100421
pmc: PMC9293079
doi:
Substances chimiques
Alkadienes
0
Acyl-CoA Dehydrogenases
EC 1.3.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3173-3177Subventions
Organisme : Germany Research Foundation DFG within RTG 1976
ID : 235777276
Organisme : SPP1319 program
ID : 222/5-1
Informations de copyright
© 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH.
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