Light is essential for life. It powers photosynthesis, sets the rhythms of day and night, and provides organisms with crucial information about their environment. But sunlight can also be dangerous. Excessive exposure can damage cells and disrupt essential biological processes, so living organisms have evolved sophisticated ways to sense light and respond quickly to it. Some bacteria have developed an especially surprising strategy: they use vitamin B 12 as a light sensor, a molecule otherwise best known for its role in metabolism where it helps enzymes carry out chemical reactions thermally.
Our recent work [1] focused on understanding how this unusual B12 light-sensing is orchestrated within a bacterial photoreceptor protein called CarH. This protein acts as a molecular switch that helps bacteria respond to sunlight. In darkness, CarH binds to DNA and prevents the production of protective pigments. When exposed to light, the protein undergoes structural changes that release the DNA, allowing the bacteria to produce carotenoids that act like a natural sunscreen. Although this mechanism was known, the exact molecular events linking light absorption to this biological response remained unclear. Using a combination of advanced structural biology at large facilities such as synchrotrons and X-ray free-electron lasers (XFEL), time-resolved spectroscopy, and quantum chemical calculations, we captured photoactivation events in unprecedented detail, following them from billionths of a second after light absorption all the way to the slower structural rearrangements that occur over seconds (Figure 1).
Our study revealed that when CarH absorbs light, a chemical bond within the B12 molecule breaks within less than 10 ns. This triggers the formation of a previously unknown intermediate state in which the photolytically cleaved part of vitamin B12 temporarily reconnects to the cobalt atom at a different position (3 μs). This unexpected molecular “bridge” turns out to be crucial: it directs the process, connecting the ultrafast chemistry triggered by light to the much slower protein motions needed to activate the biological response. Beyond answering a longstanding biological question, this work opens exciting possibilities for biotechnology, it offers a promising platform for developing new optogenetic tools (systems that use light to control biological processes with high precision). Besides using XFELs at SACLA and SwissFEL for atomic-resolution snapshots of CarH during photoactivation (Figure 1i-iv), the research heavily relied on access to several ESRF beamlines. In particular, beamline ID09 was used to obtain kinetic and low- resolution structural information by time-resolved X-ray solution scattering (Figure 1a,b). BM07 (FIP2) and the icOS platform were used to cryo-trap and characterize a photointermediate that resembles the one captured at room temperature at 3 μs (Figure 1iii). Furthermore, ID30A-1, ID30A-3, ID23-1 and ID23-2 were used for crystal screening and characterization.
This research highlights how evolution can adapt even the most familiar molecules for entirely new purposes, transforming vitamin B 12 from a metabolic cofactor into a sophisticated light sensor that helps bacteria survive in changing environments.
R. Rios-Santacruz (IBS), K. Pounot (ESRF), N. Coquelle (IBS), S. Schianchi (IBS), S. Engilberge (IBS), M. Levantino (ESRF), A. Royant (IBS/ESRF), M. Weik (IBS), G. Schirò (IBS)
[1] Rios-Santacruz R, Poddar H, Pounot K, Heyes DJ et al. (2026) Nature, 650, 1045-1052.
Figure 1: Spatiotemporal photoactivation mechanism of CarH. (a) In the dark, CarH assembles as a tetramer, with each monomer comprising two domains that bind vitamin B12 in between. In the dark state (i) the photolabile bond between the Co atom and the C5′atom is well-defined. Following green light photoexcitation, sequential photointermediates (ii–iv) are formed, these include a bi-radical state at 10 ns after photolysis of the bond (ii), a Co–C4′ adduct at 3 μs (iii) and a mono-histidine state at 10 ms (iv) to finally end in the light state (v) associated with tetramer dissociation (b). Time constants (0.5 μs, 7 ms and 0.6 s) for the transitions between species ii–v are indicated.
