UC Santa Barbara

Catechol-functionalized biomolecules are pervasive in biology, owing to their ability to mediate interactions with metal ions and mineral surfaces, among other functions. Microbes have leveraged the chemistry of catechol in the form of catechol siderophores, which bind and sequester ferric iron under conditions of nutrient stress. Tidal-dwelling marine organisms like the common mussel, Mytilus edulis, adhere to underwater surfaces through secretion of L-Dopa-functionalized proteins, harnessing the adhesive properties of catechol.Metal complexes of tris(bidentate) ligands can exist in either the Δ or Λ configuration, depending on the helical arrangement of the ligands around the metal center. Many triscatecholate siderophores bind iron in a stereospecific fashion to form coordination complexes of a defined chirality. The factors guiding this configurational preference will be discussed and the biological consequences presented herein. Frederiksenibactin, linear-(DHB-LLys-LSer)3, was isolated and characterized following the identification of an uncharacterized biosynthetic gene cluster in Yersinia frederiksenii ATCC 33641. Frederiksenibactin is notable in that it is nearly diastereomeric to the known siderophore, cyclic trichrysobactin, consisting of the macrolactone trimer of LSer, DLys, and 2,3-dihydroxybenzoic acid. Furthermore, ferric complexes of frederiksenibactin and cyclic trichrysobactin form complexes of the opposing configurational preference around Fe(III). Stereochemical isomers of these siderophores were synthesized and the corresponding Fe(III) complexes were characterized by circular dichroism spectroscopy to determine the factors dictating the configurational preference at iron. Trivanchrobactin, the triscatecholate siderophore produced by V. campbellii DS40M4, binds iron exclusively in the Λ configuration. The diastereomer of trivanchrobactin, ruckerbactin, is produced by a competing bacterial strain, and forms the opposing Δ complex. We find that the trivanchrobactin utilization pathway is stereospecific and is selective for Λ-ferric triscatecholate complexes. Transport assays reveal that chiral recognition occurs at the level of specific outer membrane receptor proteins, resulting in significantly diminished uptake of Fe(III)-ruckerbactin relative to Fe(III)-trivanchrobactin. Catechol-containing small molecule wet adhesive compounds inspired by mussel foot proteins were additionally synthesized. This work explores the practical limitations of catechol-based adhesives and the potential benefits of using alternate metal binding functionalities. Substitution of the catechol functionalities for 1,2-hydroxypyridinone (1,2-HOPO) significantly improved the adhesion to mica at neutral pH, as well as the stability of the adhesive molecules in solution. These advantages are hypothesized to be due to the superior oxidative stability of 1,2-HOPO relative to catechol, which is known to undergo facile oxidation in aerobic environments.