UC Santa Barbara

Iron is an essential nutrient for virtually all life on earth. Bacteria often live in highly iron-limiting conditions such as the ocean, where iron levels are naturally low and where bioavailable iron is hindered by the favorable formation of insoluble iron oxides, or in mammalian hosts where iron is sequestered within in iron-binding proteins. To survive, bacteria often make small-molecule Fe(III) chelators called siderophores. The biosynthesis of siderophores is hard-coded in bacterial genomes, and siderophore structures can be estimated by analyzing similar biosynthetic genes. Aside from a primary function of iron transport, some siderophores show a wide range of unique reactivities, including in particular, photoreactivity.Reported herein is the discovery of a new suite of citrate-based siderophores named the woodybactins, isolated from the bioluminescent marine bacterium Shewanella woodyi MS32. The structures of the woodybactins were partially predicted through genome mining. The prediction, isolation, and structural viii characterization of the woodybactins is discussed. Notably, the absence of a key siderophore biosynthetic gene in the vicinity of the biosynthetic gene cluster leads to a unique ‘asymmetric’ structure. Also presented herein are investigations into the photoreactivity of the siderophores gramibactin and gramibactin B produced by Paraburkholderia graminis DSM 17151. These siderophores contain a C-diazeniumdiolate functional group, a newly discovered Fe(III)-binding ligand in siderophores. While C- diazeniumdiolates have been demonstrated to enzymatically release nitric oxide (NO)—a molecule with a wide variety of applications ranging from plant growth to medicinal uses—few studies have investigated the photorelease of NO from C- diazeniumdiolates. Gramibactin and gramibactin B each release two equivalents of NO when irradiated with ultraviolet light. NO release was determined by qualitative and quantitative applications of the Griess Assay combined with mass spectrometry studies of both unlabeled and 15N-labeled gramibactins. Additionally, the photochemistry of gramibactin bound to Fe(III) and Ga(III) is reported, as well as preliminary investigations into Cu(II) coordination.