The role of extended Fe4S4 cluster ligands in mediating sulfite reductase hemoprotein activity

Cepeda, Marisa R.; McGarry, Lauren; Pennington, Joseph M.; Krzystek, J.; Stroupe, M. Elizabeth

doi:10.1016/j.bbapap.2018.05.013

Cited by 3 publications

(1 citation statement)

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“…The sulfur metabolism pathways of strain DSM 7029 predicted by KEGG revealed that four genes in this operon are involved in sulfate reduction and assimilation (Additional file 1: Figure S10). Therefore, we concluded that Fdx_0135 and FdR_0130 may constitute a pair of electron transfer partners that deliver electrons to sulfite reductase and that FdR_7100 may be a prevalent redox protein supporting the physiological function of DSM 7029 [29].…”

Section: Discussionmentioning

confidence: 92%

Heterologous redox partners supporting the efficient catalysis of epothilone B biosynthesis by EpoK in Schlegelella brevitalea

et al. 2020

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Background Epothilone B is a natural product that stabilizes microtubules, similar to paclitaxel (Taxol); therefore, epothilone B and several derivatives have shown obvious antitumour activities. Some of these products are in clinical trials, and one (ixabepilone, BMS) is already on the market, having been approved by the FDA in 2007. The terminal step in epothilone B biosynthesis is catalysed by the cytochrome P450 enzyme EpoK (CYP167A1), which catalyses the epoxidation of the C12–C13 double bond (in epothilone C and D) to form epothilone A and B, respectively. Although redox partners from different sources support the catalytic activity of EpoK in vitro, the conversion rates are low, and these redox partners are not applied to produce epothilone B in heterologous hosts. Results Schlegelella brevitalea DSM 7029 contains electron transport partners that efficiently support the catalytic activity of EpoK. We screened and identified one ferredoxin, Fdx_0135, by overexpressing putative ferredoxin genes in vivo and identified two ferredoxin reductases, FdR_0130 and FdR_7100, by whole-cell biotransformation of epothilone C to effectively support the catalytic activity of EpoK. In addition, we obtained strain H7029-3, with a high epothilone B yield and found that the proportion of epothilone A + B produced by this strain was 90.93%. Moreover, the whole-cell bioconversion strain 7029-10 was obtained; this strain exhibited an epothilone C conversion rate of 100% in 12 h. Further RT-qPCR experiments were performed to analyse the overexpression levels of the target genes. Gene knock-out experiments showed that the selected ferredoxin (Fdx_0135) and its reductases (FdR_0130 and FdR_7100) might participate in critical physiological processes in DSM 7029. Conclusion Gene overexpression and whole-cell biotransformation were effective methods for identifying the electron transport partners of the P450 enzyme EpoK. In addition, we obtained an epothilone B high-yield strain and developed a robust whole-cell biotransformation system. This strain and system hold promise for the industrial production of epothilone B and its derivatives.

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Section: Discussionmentioning

confidence: 92%

Heterologous redox partners supporting the efficient catalysis of epothilone B biosynthesis by EpoK in Schlegelella brevitalea

et al. 2020

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Molecular understanding of heteronuclear active sites in heme–copper oxidases, nitric oxide reductases, and sulfite reductases through biomimetic modelling

et al. 2021

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The bio-relevant metals of the periodic table of the elements

Sigel

2019

Zeitschrift Für Naturforschung B

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The bio-relevant metals (and derived compounds) of the Periodic Table of the Elements (PTE) are in the focus. The bulk elements sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca) from the s-block, which are essential for all kingdoms of life, and some of their bio-activities are discussed. The trace elements of the d-block of the PTE as far as they are essential for humans (Mn, Fe, Co, Cu, Zn, Mo) are emphasized, but V, Ni, Cd, and W, which are essential only for some forms of life, are also considered. Chromium is no longer classified as being essential. From the p-block metals only the metalloid (half-metal) selenium (Se) is essential for all forms of life. Two other metalloids, silicon and arsenic, are briefly mentioned, but they have not been proven as being essential for humans. All metals of the PTE and a plethora of their compounds are used in industry and many of them are highly toxic, like lead (Pb), which is discussed as a prime example. Several metals of the PTE, that is, their ions and complexes, are employed in medicine and we discuss the role of lithium, gallium, strontium, technetium, silver, gadolinium (the only f-block element), platinum, and gold.

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The role of extended Fe4S4 cluster ligands in mediating sulfite reductase hemoprotein activity

Cited by 3 publications

References 30 publications

Heterologous redox partners supporting the efficient catalysis of epothilone B biosynthesis by EpoK in Schlegelella brevitalea

Heterologous redox partners supporting the efficient catalysis of epothilone B biosynthesis by EpoK in Schlegelella brevitalea

Molecular understanding of heteronuclear active sites in heme–copper oxidases, nitric oxide reductases, and sulfite reductases through biomimetic modelling

The bio-relevant metals of the periodic table of the elements

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