Methanotrophy, Methylotrophy, the Human Body and Disease

Methylotrophic Bacteria use one-carbon (C1) compounds as their carbon source. They have been known to be associated to the human body for almost 20 years as part of the normal flora and were identified as pathogens in the early 1990s in end-stage HIV patients and chemotherapy patients. In this chapter, I look at C1 compounds in the human body and exposure from the environment and then consider Methylobacterium spp. and Methylorubrum spp. in terms of infections, its role in breast and bowel cancers; Methylococcus capsulatus and its role in inflammatory bowel disease, and Brevibacterium casei and Hyphomicrobium sulfonivorans as part of the normal human flora. I also consider the abundance of methylotrophs from the Actinobacteria being identified in human studies and the potential bias of the ionic strength of culture media and the needs for future work. Within the scope of future work, I consider the need for the urgent assessment of the pathogenic, oncogenic, mutagenic and teratogenic potential of Methylobacterium spp. and Methylorubrum spp. and the need to handle them at higher containment levels until more data are available

Advanced Paramagnetic Resonance Studies on Manganese and Iron Corroles with a Formal d(4) Electron Count

Metallocorroles wherein the metal ion is Mn-III and formally Fe-IV are studied here using field- and frequency-domain electron paramagnetic resonance techniques. The Mn-III corrole, Mn(tpfc) (tpfc = 5,10,15-tris(pentafluorophenyl)corrole trianion), exhibits the following S = 2 zero-field splitting (zfs) parameters: D = 2.67(1) cm(-1), 1E1 = 0.023(5) cm-1. This result and those for other Mn-III tetrapyrroles indicate that when D = 2.5 0.5 cm(-1) for 4- or 5 coordinate and D 3.5 0.5 cm(-1) for 6-coordinate complexes, the ground state description is [Mn111(Cor3-)] or [Mn111(P2-)]+ (Cor = corrole, P = porphyrin). The situation for formally Few corroles is more complicated, and it has been shown that for Fe(Cor)X, when X = Ph (phenyl), the ground state is a spin triplet best described by [Few(Cor(3)(-))]+, but when X = halide, the ground state corresponds to [Fe-III(Cor(2)(-))]+, wherein an intermediate spin (S = 3/2) Fe-III is antiferromagnetically coupled to a corrole radical dianion (S = 1/2) to also give an S = 1 ground state. These two valence isomers can be distinguished by their zfs parameters, as determined here for Fe(tpc)X, X = Ph, Cl (tpc = 5,10,15 triphenylcorrole trianion). The complex with axial phenyl gives D = 21.1(2) cm(-1), while that with axial chloride gives D = 14.6(1) cm(-1). The D value for Fe(tpc)Ph is in rough agreement with the range of values reported for other Few complexes. In contrast, the D value for Fe(tpc)Cl is inconsistent with an Felv description and represents a different type of iron center. Computational studies corroborate the zfs for the two types of iron corrole complexes. Thus, the zfs of metallocorroles can be diagnostic as to the electronic structure of a formally high oxidation state metallocorrole, and by extension to metalloporphyrins, although such studies have yet to be performed

Characterization of Iron Dinitrosyl Species Formed in the Reaction of Nitric Oxide with a Biological Rieske Center

Reactions of nitric oxide with cysteine-ligated iron−sulfur cluster proteins typically result in disassembly of the iron−sulfur core and formation of dinitrosyl iron complexes (DNICs). Here we report the first evidence that DNICs also form in the reaction of NO with Rieske-type [2Fe-2S] clusters. Upon treatment of a Rieske protein, component C of toluene/o-xylene monooxygenase from Pseudomonas sp. OX1, with an excess of NO(g) or NO-generators S-nitroso-N-acetyl-d,l-pencillamine and diethylamine NONOate, the absorbance bands of the [2Fe-2S] cluster are extinguished and replaced by a new feature that slowly grows in at 367 nm. Analysis of the reaction products by electron paramagnetic resonance, Mössbauer, and nuclear resonance vibrational spectroscopy reveals that the primary product of the reaction is a thiolate-bridged diiron tetranitrosyl species, [Fe[subscript 2](μ-SCys)[subscript 2](NO)[subscript 4]], having a Roussin’s red ester (RRE) formula, and that mononuclear DNICs account for only a minor fraction of nitrosylated iron. Reduction of this RRE reaction product with sodium dithionite produces the one-electron-reduced RRE, having absorptions at 640 and 960 nm. These results demonstrate that NO reacts readily with a Rieske center in a protein and suggest that dinuclear RRE species, not mononuclear DNICs, may be the primary iron dinitrosyl species responsible for the pathological and physiological effects of nitric oxide in such systems in biology.National Institute of General Medical Sciences (U.S.) (grant GM032134)United States. Dept. of Energy (DOE OBER)National Institute of General Medical Sciences (U.S.) (GM065440)National Institutes of Health (U.S.). Biotechnology Training Fellowship (Grant T32 GM08334)National Institute of General Medical Sciences (U.S.) (1 F32 GM082031-03