Fluorine is the thirteenth most abundant element in the earth's crust, but fluoride concentrations in surface water are low and fluorinated metabolites are extremely rare. The fluoride ion is a potent nucleophile in its desolvated state, but is tightly hydrated in water and effectively inert. Low availability and a lack of chemical reactivity have largely excluded fluoride from biochemistry: in particular, fluorine's high redox potential precludes the haloperoxidase-type mechanism used in the metabolic incorporation of chloride and bromide ions. But fluorinated chemicals are growing in industrial importance, with applications in pharmaceuticals, agrochemicals and materials products. Reactive fluorination reagents requiring specialist process technologies are needed in industry and, although biological catalysts for these processes are highly sought after, only one enzyme that can convert fluoride to organic fluorine has been described. Streptomyces cattleya can form carbon-fluorine bonds and must therefore have evolved an enzyme able to overcome the chemical challenges of using aqueous fluoride. Here we report the sequence and three-dimensional structure of the first native fluorination enzyme, 5'-fluoro-5'-deoxyadenosine synthase, from this organism. Both substrate and products have been observed bound to the enzyme, enabling us to propose a nucleophilic substitution mechanism for this biological fluorination reaction.

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The metabolic profile of Streptomyces sp. strain C34, isolated from the Chilean hyper-arid Atacama Desert soil, is dependent on the culture media used for its growth. The application of an OSMAC approach on this strain using a range of cultivation media resulted in the isolation and identification of three new compounds from the rare class of 22-membered macrolactone polyketides, named chaxalactins A-C (1-3). In addition, the known compounds deferroxamine E (4), hygromycin A (5), and 5″-dihydrohygromycin A (6) were detected. The isolated compounds were characterized by NMR spectroscopy and accurate mass spectrometric analysis. Compounds 1-3 displayed strong activity against Gram-positive but weak activity Gram-negative strains tested.

Streptomyces sp. strain C34, isolated from soil collected in the Chilean hyper-arid Atacama Desert, was cultured on different media, resulting in the isolation and identification of four new ansamycin-type polyketides. The organism was selected for chemical investigation on the basis of a genome-mining PCR-based experiment targeting the gene encoding rifamycin-specific 3-amino-5-hydroxybenzoic acid synthetase (AHBA). The isolated compounds were structurally characterized using NMR and MS techniques and named chaxamycins A-D (1-4). Compounds 1-4 were tested for their antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 and for their ability to inhibit the intrinsic ATPase activity of the heat shock protein 90 (Hsp90). Chaxamycin D (4), which showed a selective antibacterial activity against S. aureus ATCC 25923, was tested further against a panel of MRSA clinical isolates. In a virtual screening experiment, chaxamycins A-D (1-4) have also been docked into the ATP-binding pocket in the N-terminal domain of the Hsp90, and the observed interactions are discussed.

NIR-II fluorophores have shown great promise for biomedical applications with superior in vivo optical properties. To date, few small-molecule NIR-II fluorophores have been discovered with donor-acceptor-donor (D-A-D) or symmetrical structures, and upconversion-mitochondria-targeted NIR-II dyes have not been reported. Herein, we report development of D-A type thiopyrylium-based NIR-II fluorophores with frequency upconversion luminescence (FUCL) at ~580 nm upon excitation at ~850 nm. H4-PEG-PT can not only quickly and effectively image mitochondria in live or fixed osteosarcoma cells with subcellular resolution at 1 nM, but also efficiently convert optical energy into heat, achieving mitochondria-targeted photothermal cancer therapy without ROS effects. H4-PEG-PT has been further evaluated in vivo and exhibited strong tumor uptake, specific NIR-II signals with high spatial and temporal resolution, and remarkable NIR-II image-guided photothermal therapy. This report presents the first D-A type thiopyrylium NIR-II theranostics for synchronous upconversion-mitochondria-targeted cell imaging, in vivo NIR-II osteosarcoma imaging and excellent photothermal efficiency.