Substrate activation by iron superoxo intermediates

Donk, Wilfred A. van der; Krebs, Carsten; Bollinger, J. Martin

doi:10.1016/j.sbi.2010.08.005

Cited by 112 publications

(101 citation statements)

References 51 publications

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“…First, LA binds to the ferrous iron of the enzyme through its carboxylate moiety and organizes the iron center to coordinate molecular oxygen. This sequential binding is similar to that in many other nonheme iron enzymes, such as naphthalene dioxygenase and superoxide reductase (18,20,(23)(24)(25)(26). Next, O 2 binds, generating a putative Fe(III)-superoxide complex that abstracts the unactivated β-hydrogen of LA.…”

Section: Discussionmentioning

confidence: 54%

Microbial biosynthesis of medium-chain 1-alkenes by a nonheme iron oxidase

Rui

Zhu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

190

233

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Aliphatic medium-chain 1-alkenes (MCAEs, ∼10 carbons) are "drop-in" compatible next-generation fuels and precursors to commodity chemicals. Mass production of MCAEs from renewable resources holds promise for mitigating dependence on fossil hydrocarbons. An MCAE, such as 1-undecene, is naturally produced by Pseudomonas as a semivolatile metabolite through an unknown biosynthetic pathway. We describe here the discovery of a single gene conserved in Pseudomonas responsible for 1-undecene biosynthesis. The encoded enzyme is able to convert medium-chain fatty acids (C10-C14) into their corresponding terminal olefins using an oxygen-activating, nonheme iron-dependent mechanism. Both biochemical and X-ray crystal structural analyses suggest an unusual mechanism of β-hydrogen abstraction during fatty acid substrate activation. Our discovery unveils previously unidentified chemistry in the nonheme Fe(II) enzyme family, provides an opportunity to explore the biology of 1-undecene in Pseudomonas, and paves the way for tailored bioconversion of renewable raw materials to MCAE-based biofuels and chemical commodities.urging energy consumption and environmental concerns have stimulated interest in the production of chemicals and fuels through sustainable and renewable approaches. Medium-chain 1-alkenes (MCAEs) are of particular interest because they are "drop-in"-ready next-generation fuels with superior properties such as low freezing point compared with long-chain diesels, high energy content compared with short-chain fuels, easy product recovery due to insolubility in water, and compatibility with the existing engine systems and transportation infrastructure (1, 2). Because of a readily derivatized terminal functionality, MCAEs are also valuable precursors to commodity chemicals such as lubricants, pesticides, polymers, and detergents (3, 4). Biological production of MCAEs from renewable resources holds promise for mitigating dependence on fossil hydrocarbons. Although MCAEs are naturally produced by diverse species as semivolatile metabolites (5, 6), little is known about the genetic and molecular basis for MCAE biosynthesis. Elucidation of MCAE biosynthetic pathway will serve as the basis for engineering efforts to establish bioprocesses for producing MCAE-based biofuels and chemical commodities from renewable resources.1-Undecene, an MCAE with 11 carbons, was identified as a biomarker of Pseudomonas aeruginosa, one of the most significant human pathogens (7-10). However, the biology of this characteristic semivolatile metabolite in P. aeruginosa remains enigmatic, and the biosynthetic pathway of 1-undecene has not previously been explored. It was also reported that some species of Pseudomonas produce 1-undecene, whereas some species do not (8), inspiring us to use a comparative genomics approach to reveal the genetic basis for 1-undecene biosynthesis (11). It is notable that one of the major challenges for MCAE biosynthetic study is the detection and quantification of MCAE production. MCAEs, such as 1-undecene, are only ...

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Section: Discussionmentioning

confidence: 54%

Microbial biosynthesis of medium-chain 1-alkenes by a nonheme iron oxidase

Rui

Zhu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

190

233

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“…•− intermediate (26), whereas the Fe2 ion in ferric form will be used to bind the substrate as well as conduct electrons to Fe1 during CP bond cleavage (17).…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of PhnZ in complex with substrate reveals a di-iron oxygenase mechanism for catabolism of organophosphonates

Staalduinen

McSorley

Schiessl

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

118

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Significance Inorganic phosphate (Pi) is an essential component of many biological molecules and thus is required by all life forms. However, soluble Pi is typically at low abundance in the environment. To compensate, microbes have evolved unique carbon–phosphorus-bond cleaving reactions to use organophosphonates as an alternative source of Pi. The marine-derived enzyme PhnZ utilizes a new oxidative mechanism for CP bond cleavage involving iron and molecular oxygen. The three-dimensional structure of PhnZ reveals unique active site features that contribute to catalysis of CP bond cleavage and substrate specificity, as well as an evolutionary link between phosphodiester bond hydrolysis and oxidative bond cleavage. This evolutionary link likely reflects the ancient origins of organophosphonates in the environment.

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“…[1][2][3][4] Such a step has been proposed for many aromatic and aliphatic C À C bond cleaving dioxygenases. [1,5] Recently discovered examples include 2-hydroxyethylphosphonate (HEP) dioxygenase (HEPD) which catalyzes the cleavage of the HEP C1ÀC2 bond to form hydroxymethylphosphonate and formate, [3] and CloR, which is involved in the conversion of a mandelate moiety to benzoate in the biosynthesis of chlorobiocin, an aminocoumarin antibiotic. [6] For the above examples, the substrate provides all four electrons needed for the reduction of O 2 to water.…”

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confidence: 99%