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By Kimie Nakagawa and colleagues. Nature 468, 117–121 (2010). DOI doi.org/10.1038/nature09464

Abstract and Figures 1–3: isotope-labelled vitamin-K derivatives, UBIAD1 knockdown in human cells, expression in insect cells, and deuterium NMR identification of menaquinone-4.

Kimie Nakagawa investigated Vitamin K metabolism, including how cells make menaquinone-4. A 2010 study identified UBIAD1 as a human biosynthetic enzyme using complementary perturbation and expression experiments.^[ref]

Reducing UBIAD1 expression with siRNA decreased formation of isotope-labelled menaquinone-4 in human cells. Expression in insect cells provided a second test, and deuterium nuclear magnetic resonance checked the product's identity. Combining altered production with chemical identification is stronger evidence for a biosynthetic role than similarity of protein sequences alone.^[ref]

A prenyltransferase is an enzyme that transfers a prenyl group, an isoprenoid-derived carbon group, to an acceptor. The term covers multiple reactions; the acceptor can be a small molecule rather than a protein. It should therefore not be interpreted as meaning only an enzyme for protein prenylation.

One concrete reaction joins the five-carbon dimethylallyl diphosphate and five-carbon isopentenyl diphosphate to make ten-carbon geranyl diphosphate, releasing diphosphate. Carbon counting gives $5+5=10$, while the substrate names specify the activated donors and the product structure. The official entry for this enzyme also notes poor acceptance of larger prenyl diphosphates as donors: a generic transfer label does not imply unrestricted substrate choice.^[ref]

A different example links this chemistry to Vitamin K. In 2010, Kimie Nakagawa and colleagues identified UBIAD1 as an enzyme for menaquinone-4 biosynthesis. Reducing its expression suppressed conversion of deuterium-labelled vitamin-K derivatives into labelled product; expression in insect cells restored a production system, and nuclear magnetic resonance helped identify the product.^[ref] Combining perturbation with chemical identification provides stronger evidence for an enzyme assignment than finding a similar-looking gene sequence alone.