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Multicomponent reactions – those where three or more substrates combine into a product – have been highly useful in rapidly building chemical building blocks of increased complexity⁴, but achieving this enzymatically has remained rare.⁵ This limitation primarily arises because an enzyme’s active site is not typically set up to address multiple substrates, especially in cases involving multiple radical intermediates⁶. Recently, chemical catalytic radical sorting has emerged as an enabling strategy for a variety of useful reactions^7,8. However, making such processes enantioselective is highly challenging due to the inherent difficulty in the stereochemical control of radicals⁹. Here, we repurpose a thiamine-dependent enzyme^10,11 through directed evolution, combine it with photoredox catalysis, to achieve a photobiocatalytic enantioselective three-component radical cross-coupling. This approach combines three readily available starting materials — aldehydes, α-bromo-carbonyls and alkenes — to give access to enantioenriched ketone products. Mechanistic investigations provide insights into how this dual photo-/enzyme system precisely directs the three distinct radicals involved in the transformation, unlocking new enzyme reactivity. Our approach has achieved exceptional stereoselectivity, with 25 out of 33 examples achieving ≥97% enantiomeric excess.

C₄ photosynthesis is used by the most productive plants on the planet, and compared with the ancestral C₃ pathway, it confers a 50% increase in efficiency¹. In more than 60 C₄ lineages, CO₂ fixation is compartmentalized between tissues, and bundle-sheath cells become photosynthetically activated². How the bundle sheath acquires this alternate identity that allows efficient photosynthesis is unclear. Here we show that changes to bundle-sheath gene expression in C₄ leaves are associated with the gain of a pre-existing cis-code found in the C₃ leaf. From single-nucleus gene-expression and chromatin-accessibility atlases, we uncover DNA binding with one finger (DOF) motifs that define bundle-sheath identity in the major crops C₃ rice and C₄ sorghum. Photosynthesis genes that are rewired to be strongly expressed in the bundle-sheath cells of C₄ sorghum acquire cis-elements that are recognized by DOFs. Our findings are consistent with a simple model in which C₄ photosynthesis is based on the recruitment of an ancestral cis-code associated with bundle-sheath identity. Gain of such elements harnessed a stable patterning of transcription factors between cell types that are found in both C₃ and C₄ leaves to activate photosynthesis in the bundle sheath. Our findings provide molecular insights into the evolution of the complex C₄ pathway, and might also guide the rational engineering of C₄ photosynthesis in C₃ crops to improve crop productivity and resilience^3,4.

Animals are often bombarded with visual information and must prioritize specific visual features based on their current needs. The neuronal circuits that detect and relay visual features have been well studied^{1,2,3,4,5,6,7,8}. Much less is known about how an animal adjusts its visual attention as its goals or environmental conditions change. During social behaviours, flies need to focus on nearby flies^9,10,11. Here we study how the flow of visual information is altered when female Drosophila enter an aggressive state. From the connectome, we identify three state-dependent circuit motifs poised to modify the response of an aggressive female to fly-sized visual objects: convergence of excitatory inputs from neurons conveying select visual features and internal state; dendritic disinhibition of select visual feature detectors; and a switch that toggles between two visual feature detectors. Using cell-type-specific genetic tools, together with behavioural and neurophysiological analyses, we show that each of these circuit motifs is used during female aggression. We reveal that features of this same switch operate in male Drosophila during courtship pursuit, suggesting that disparate social behaviours may share circuit mechanisms. Our study provides a compelling example of using the connectome to infer circuit mechanisms that underlie dynamic processing of sensory signals.