CYP82Y1 Is N-Methylcanadine 1-Hydroxylase, a Key Noscapine Biosynthetic Enzyme in Opium Poppy

Abstract

Background:The biochemistry of noscapine metabolism in opium poppy has not been established. Results: CYP82Y1 catalyzes the efficient 1-hydroxylation of N-methylcanadine. Silencing CYP82Y1 reduced noscapine accumulation in opium poppy plants. Conclusion: CYP82Y1 is N-methylcanadine 1-hydroxylase and functions in noscapine biosynthesis. Significance: The enzyme catalyzing the first step in the conversion of N-methylcanadine to noscapine has been identified and characterized.

Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy

“…Other CYP82 members catalyze ring hydroxylations in benzylisoquinoline alkaloid biosynthesis [15][16][17][18] . Desaturation is not a common CYP function in plants, although sterol desaturases 19,20 and desaturating flavone synthases 21 have been reported.…”

Benzylisoquinoline alkaloid biosynthesis in opium poppy

“…The function of metabolic gene clusters in plants has been suggested as a mechanism to regulate expression at the epigenetic level (wegel et al 2009) and to facilitate complete inheritance of a specialized metabolic pathway (Swaminathan et al 2009). Recently, CAS (Dang and Facchini 2014a), N-methylcanadine 1-hydroxylase (CYP82Y1) (Dang and Facchini 2014b) and noscapine synthase (NOS) (Chen and Facchini 2014) were isolated and characterized from opium poppy. NOS was characterized as a NAD + -dependent, short-chain dehydrogenase/ reductase catalyzing the irreversible conversion of narcotinehemiacetal to noscapine.…”

Acetylation serves as a protective group in noscapine biosynthesis in opium poppy

“…1). CYP82X2 and CYP82X1 have been predicted to act downstream of (S)-1-hydroxy-N-methylcanadine by catalyzing (i) C13 hydroxylation and (ii) C8 hydroxylation to break the N7-C8 bridge 8,10 . Both CYP82X1 and CYP82X2, each independently expressed together with cytochrome P450 reductase (CPR) in Saccharomyces cerevisiae (Supplementary Fig.…”