Nicotine biosynthesis module (Nicotiana / Solanaceae)

A plant-scoped, recursively decomposable decomposition of nicotine biosynthesis as it operates in Nicotiana (tobacco / wild tobacco). Nicotine is an alkaloid built by condensing two separately made rings: a PYRIDINE ring supplied by the aspartate-derived NAD/quinolinate (pyridine nucleotide) branch, and a PYRROLIDINE ring (the N-methyl-Delta1-pyrrolinium cation) supplied by the polyamine/ornithine branch. The module separates these two upstream supply branches from the late "nicotine synthase" cascade that joins the rings, and from the vacuolar transport/metabolon step. This module is intentionally NOT a flat gene list (that lives in the per-gene NICAT reviews and the NICOTINE_BIOSYNTHESIS project). Its purpose is to capture the pathway-level structure that the individual gene reviews cannot: the two-branch convergence, the recently revised late steps, and the co-clustered transport component. The late steps are phrased to reflect the 2025-2026 revision of the pathway. In the classical model the N-methylpyrrolinium cation condensed with a nicotinic acid derivative directly. The new model ("complete biosynthesis of nicotine", Cell 2026, PMID:41928514; "nicotine biosynthesis completed by cryptic activating glucosylation", Nat Commun 2026, PMID:42151135) routes nicotinic acid through a hidden N-glucosylation/reduction/condensation/deglucosylation relay: a UDP-glucosyltransferase (UGT1/NaGT) glucosylates nicotinic acid to nicotinic acid N-glucoside, an A622/NaGR reductase and a BBL oxidase act on the activated glucoside during condensation with the pyrrolidine ring, and a beta-glucosidase (beta-GD1/NicGH) removes the sugar to release nicotine. A vacuolar-membrane MATE transporter (MATE1) co-clusters with A622 and beta-GD1 and is required for high heterologous production. This activating-glucosylation relay and the A622-MATE1-beta-GD1 metabolon are the parts of the pathway that GO biological-process and molecular-function terms flatten away.

Grounding policy: GO molecular-function and biological-process identifiers were copied from the verified per-gene NICAT reviews (each harvested term is used in that gene's core_functions), so they are trusted. Metabolite/intermediate descriptors were grounded to ChEBI via EBI OLS exact-label lookup; descriptors that still lack a `term` (the N-methyl-Delta1-pyrrolinium cation, the nicotinic acid N-glucoside / reduced-glucoside intermediates, and small byproducts such as dioxygen / CO2 / ammonia / diphosphate where no unambiguous ChEBI exact match was returned) were left ungrounded rather than guessed. Representative UniProt members are the project's current sequence-backed NICAT candidate accessions (see the 2026-04-05 mapping dive in the project page); they are orienting exemplars, not official symbol normalizations and not a claim that the pathway is limited to those accessions. The NAMN-hydrolase step (NaNAMNH) and the ring-condensation step are real pathway steps for which no confident GO molecular-function id was available, so their function descriptors carry no term.