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Abstract Nitriles are uncommon in nature and are typically constructed from oximes through the oxidative decarboxylation of amino acid substrates or from the derivatization of carboxylic acids. Here we report a third nitrile biosynthesis strategy featuring the cyanobacterial nitrile synthase AetD. During the biosynthesis of the eagle-killing neurotoxin, aetokthonotoxin, AetD transforms the 2-aminopropionate portion of 5,7-dibromo-l-tryptophan to a nitrile. Employing a combination of structural, biochemical and biophysical techniques, we characterized AetD as a non-haem diiron enzyme that belongs to the emerging haem-oxygenase-like dimetal oxidase superfamily. High-resolution crystal structures of AetD together with the identification of catalytically relevant products provide mechanistic insights into how AetD affords this unique transformation, which we propose proceeds via an aziridine intermediate. Our work presents a unique template for nitrile biogenesis and portrays a substrate binding and metallocofactor assembly mechanism that may be shared among other haem-oxygenase-like dimetal oxidase enzymes. 

Monitoring the impacts of global efforts to reduce mercury (Hg) emissions is limited by the collection of biological samples at appropriate spatiotemporal scales. This is especially true in the deep sea, a vast region with food webs that cycle bioaccumulative methylmercury (MeHg). Within a species, understanding the distribution of Hg across tissue types can reveal how Hg accumulates in the body and inform how useful a species is for biomonitoring geographic regions or vertical habitats of the ocean. We focus on a globally distributed deep-sea fish, the longnose lancetfish (Alepisaurus ferox, n = 69 individuals), and measure total mercury (THg) and MeHg concentrations in 10 tissue types (brain, caudal white muscle, dorsal white muscle, gallbladder, gill filament, gonad, heart, intestine, liver, and stomach lining). Across all tissue types, THg and MeHg concentrations were higher in large lancetfish (≥1.8 kg) than small lancetfish (<1.8 kg), but concentrations were relatively stable within size classes. THg levels were highest in liver, intestine, and heart, followed by caudal white muscle, dorsal white muscle, stomach lining, and gill filament, then by gonad and gallbladder. We describe how ontogenetic diet shifts explain Hg bioaccumulation in pelagic predators inhabiting similar waters to lancetfish. We hypothesize that diet shifts to deeper-dwelling prey and fishes drive increases in THg and MeHg concentrations in large lancetfish. We propose lancetfish as a strong candidate for monitoring spatiotemporal variability of Hg in the deep pelagic – they are commonly captured in global fisheries and may reflect Hg sources in two distinct vertical habitats of the ocean. 

The bioaccumulation of methylmercury in fish and its biomagnification through the food chain is a major public health concern. Differences in fish methylmercury concentration observed between China and the United States highlight the need for a better understanding of region-specific factors that drive its formation and biological uptake.