Publications

• Biosynthesis of fluopsin C, a copper-containing antibiotic from <i>Pseudomonas aeruginosa</i>.

  Patteson J.B., Putz A.T., Tao L., Simke W.C., Bryant L.H., Britt R.D., Li B.

  Metal-binding natural products contribute to metal acquisition and bacterial virulence, but their roles in metal stress response are underexplored. We show that a five-enzyme pathway in <i>Pseudomonas aeruginosa</i> synthesizes a small-molecule copper complex, fluopsin C, in response to elevated c ... >> More

  Metal-binding natural products contribute to metal acquisition and bacterial virulence, but their roles in metal stress response are underexplored. We show that a five-enzyme pathway in <i>Pseudomonas aeruginosa</i> synthesizes a small-molecule copper complex, fluopsin C, in response to elevated copper concentrations. Fluopsin C is a broad-spectrum antibiotic that contains a copper ion chelated by two minimal thiohydroxamates. Biosynthesis of the thiohydroxamate begins with cysteine and requires two lyases, two iron-dependent enzymes, and a methyltransferase. The iron-dependent enzymes remove the carboxyl group and the α carbon from cysteine through decarboxylation, N-hydroxylation, and methylene excision. Conservation of the pathway in <i>P. aeruginosa</i> and other bacteria suggests a common role for fluopsin C in the copper stress response, which involves fusing copper into an antibiotic against other microbes. << Less

  Science 374:1005-1009(2021) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Structural Basis for Methine Excision by a Heme Oxygenase-like Enzyme.

  Simke W.C., Walker M.E., Calderone L.A., Putz A.T., Patteson J.B., Vitro C.N., Zizola C.F., Redinbo M.R., Pandelia M.E., Grove T.L., Li B.

  Heme oxygenase-like domain-containing oxidases (HDOs) are a rapidly expanding enzyme family that typically use dinuclear metal cofactors instead of heme. FlcD, an HDO from the opportunistic pathogen <i>Pseudomonas aeruginosa</i>, catalyzes the excision of an oxime carbon in the biosynthesis of the ... >> More

  Heme oxygenase-like domain-containing oxidases (HDOs) are a rapidly expanding enzyme family that typically use dinuclear metal cofactors instead of heme. FlcD, an HDO from the opportunistic pathogen <i>Pseudomonas aeruginosa</i>, catalyzes the excision of an oxime carbon in the biosynthesis of the copper-containing antibiotic fluopsin C. We show that FlcD is a dioxygenase that catalyzes a four-electron oxidation. Crystal structures of FlcD reveal a mononuclear iron in the active site, which is coordinated by two histidines, one glutamate, and the oxime of the substrate. Enzyme activity, Mössbauer spectroscopy, and electron paramagnetic resonance spectroscopy analyses support the usage of a mononuclear iron cofactor. This cofactor resembles that of mononuclear non-heme iron-dependent enzymes and breaks the paradigm of dinuclear HDO cofactors. This study begins to illuminate the catalytic mechanism of methine excision and indicates convergent evolution of different lineages of mononuclear iron-dependent enzymes. << Less

  ACS Cent Sci 10:1524-1536(2024) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.