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Abstract

Monoterpene indole alkaloids, a large class of plant natural products, derive from the biosynthetic intermediate strictosidine
aglycone. Strictosidine aglycone, which can exist as a variety of
isomers, can be reduced to form numerous different structures. We
have discovered a short chain alcohol dehydrogenase (SDR) from
monoterpene indole alkaloid producing plants (Catharanthus roseus
and Rauvolfia serpentina) that reduce strictosidine aglycone and
produce an alkaloid that does not correspond to any previously
reported compound. Here we report the structural characterization of
this product, which we have named vitrosamine, as well as the crystal
structure of the SDR. This discovery highlights the structural versatility
of the strictosidine aglycone biosynthetic intermediate and expands
the range of enzymatic reactions that SDRs can catalyze. This
discovery further highlights how a sequence-based gene mining
discovery approach in plants can reveal cryptic chemistry that would
not be uncovered by classical natural product chemistry approaches