Language:
English
In:
Science (American Association for the Advancement of Science), 2015-07-17, Vol.349 (6245), p.309-312
Description:
Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.
Subject(s):
Biosynthesis ; Enzymes ; Metabolites ; Modules ; Morphine ; Narcotics ; Pathways ; Poppies ; Proteins ; REPORTS
ISSN:
0036-8075
E-ISSN:
1095-9203
DOI:
10.1126/science.aab1852
Source:
JSTOR Life Sciences
Source:
Academic Search Ultimate
Source:
Alma/SFX Local Collection
Source:
Get It Now
