Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.10.3.2 (
laccase
)
4,656
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Perylenequinones are a class of aromatic polyketides characterised by a highly conjugated pentacyclic core, which confers them with potent light-induced bioactivities and unique photophysical properties. Despite the biosynthetic gene clusters for the perylenequinones elsinochrome A (
1
), cercosporin (
4
) and hypocrellin A (
6
) being recently identified, key biosynthetic aspects remain elusive. Here, we first expressed the intact
elc
gene cluster encoding
1
from the wheat pathogen
Parastagonospora nodorum
heterologously in
Aspergillus nidulans
on a yeast-fungal artificial chromosome (YFAC). This led to the identification of a novel flavin-dependent monooxygenase, ElcH, responsible for oxidative enolate coupling of a perylenequinone intermediate to the hexacyclic dihydrobenzo(
ghi
)perylenequinone in
1
. In the absence of ElcH, the perylenequione intermediate formed a hexacyclic cyclohepta(
ghi
)perylenequinone system
via
an intramolecular aldol reaction resulting in
6
and a novel hypocrellin
12
with opposite helicity to
1
. Theoretical calculations supported that
6
and
12
resulted from atropisomerisation upon formation of the 7-membered ring. Using a bottom-up pathway reconstruction approach on a tripartite YFAC system developed in this study, we uncovered that both a
berberine bridge enzyme
-like oxidase ElcE and a
laccase
-like multicopper oxidase ElcG are involved in the double coupling of two naphthol intermediates to form the perylenequinone core. Gene swapping with the homologs from the biosynthetic pathway of
4
showed that cognate pairing of the two classes of oxidases is required for the formation of the perylenequinone core, suggesting the involvement of protein-protein interactions.
...
PMID:Heterologous biosynthesis of elsinochrome A sheds light on the formation of the photosensitive perylenequinone system. 3080 63
