(GQR42/OOL1) Ordering-Selected Emergence of Flavin Cofactors under Enzyme-Free Environmental Cycling

The pre-enzymatic emergence of metabolic cofactors remains a central open problem in
origin-of-life chemistry. Flavin cofactors (FMN/FAD) are chemically complex, redox-active, and
evolutionarily universal, yet no single enzyme-free synthesis pathway is known to be uniquely
favoured under equilibrium or yield-based reasoning. Here we show that temporal ordering alone
is sufficient to resolve this ambiguity.
Using Accessibility–Ordering Invariance (AOI), we treat environmental cycling—such as ul-
traviolet irradiation, hydration, adsorption, and shelter—not as background conditions but as
ordered accessibility windows that act as control variables. We construct an explicit and finite
flavin reaction web incorporating canonical wet-gated steps, photochemical activation channels,
and realistic photolysis sinks. Route scoring under AOI reveals that ordering collapses this
space to a single dominant backbone across exposed, sheltered, and seasonally cycled planetary
environments.
The selected backbone is characterised by ultraviolet-first activation followed by immediate
wet-phase capture via transient excited or radical flavin intermediates. Purely wet-gated routes
are ordering-neutral, while stable photoaddition products are consistently secondary and sup-
pressed once sinks are included. Competition analysis shows that the radical-mediated backbone
remains dominant across parameter sweeps, indicating a robust ordering selection rather than
fine-tuned kinetics.
These results imply that flavin cofactors could emerge without enzymes through environ-
mental ordering alone, with the environment itself acting as a sequencing agent. The analysis
yields a direct experimental prediction: under identical total ultraviolet dose and hydration time,
UV→wet ordering must produce measurably different flavin-family outcomes than wet→UV or-
dering. Full route enumeration, sink competition, and robustness analyses are provided in the
Supplementary Information and the public GQR repository [1, 2].