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Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein

Science  25 Jun 2015:

DOI: 10.1126/science.aab1852

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Abstract

Morphinan alkaloids from opium poppy are used for pain relief. 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 while the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed 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.

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