Diversification of Ferredoxins across Living Organisms

Nzuza, Nomfundo; Padayachee, Tiara; Chen, Wanping; Gront, Dominik; Nelson, David R.; Syed, Khajamohiddin

doi:10.3390/cimb43030098

Cited by 12 publications

(20 citation statements)

References 69 publications

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“…Phylogenetic analysis of P450s was carried out following the procedure described elsewhere [ 63 , 64 ]. The phylogenetic tree of P450s was constructed using protein sequences.…”

Section: Methodsmentioning

confidence: 99%

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species

et al. 2022

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Cytochrome P450 monooxygenases (CYPs/P450s) are heme thiolate proteins present in species across the biological kingdoms. By virtue of their broad substrate promiscuity and regio- and stereo-selectivity, these enzymes enhance or attribute diversity to secondary metabolites. Actinomycetes species are well-known producers of secondary metabolites, especially Salinispora species. Despite the importance of P450s, a comprehensive comparative analysis of P450s and their role in secondary metabolism in Salinispora species is not reported. We therefore analyzed P450s in 126 strains from three different species Salinispora arenicola, S. pacifica, and S. tropica. The study revealed the presence of 2643 P450s that can be grouped into 45 families and 103 subfamilies. CYP107 and CYP125 families are conserved, and CYP105 and CYP107 families are bloomed (a P450 family with many members) across Salinispora species. Analysis of P450s that are part of secondary metabolite biosynthetic gene clusters (smBGCs) revealed Salinispora species have an unprecedented number of P450s (1236 P450s-47%) part of smBGCs compared to other bacterial species belonging to the genera Streptomyces (23%) and Mycobacterium (11%), phyla Cyanobacteria (8%) and Firmicutes (18%) and the classes Alphaproteobacteria (2%) and Gammaproteobacteria (18%). A peculiar characteristic of up to six P450s in smBGCs was observed in Salinispora species. Future characterization Salinispora species P450s and their smBGCs have the potential for discovering novel secondary metabolites.

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“…Phylogenetic analysis of P450s was carried out following the procedure described elsewhere [ 63 , 64 ]. The phylogenetic tree of P450s was constructed using protein sequences.…”

Section: Methodsmentioning

confidence: 99%

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species

et al. 2022

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“…Ferredoxins, like other Fe-S cluster proteins, are classified into different types based on the number of Fe-atoms in their cluster, such as 2Fe-2S, 3Fe-4S, 4Fe-4S, 7Fe-8S (3Fe-4S and 4Fe-4S) and 2[4Fe-4S]) [ 29 ]. Ferredoxins are further classified into subtypes based on the characteristic spacing between the cysteine amino acids of the Fe-S binding motif [ 34 ]. A recent study provided preliminary information on ferredoxins in archaea [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…Ferredoxins are further classified into subtypes based on the characteristic spacing between the cysteine amino acids of the Fe-S binding motif [ 34 ]. A recent study provided preliminary information on ferredoxins in archaea [ 34 ]. The research showed that several archaeal ferredoxin subtypes are also present in bacteria and eukarya [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Evolution of Cytochrome P450 Enzymes and Their Redox Partners in Archaea

Ngcobo

Nkosi

Chen

et al. 2023

IJMS

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Cytochrome P450 monooxygenases (CYPs/P450s) and their redox partners, ferredoxins, are ubiquitous in organisms. P450s have been studied in biology for over six decades owing to their distinct catalytic activities, including their role in drug metabolism. Ferredoxins are ancient proteins involved in oxidation-reduction reactions, such as transferring electrons to P450s. The evolution and diversification of P450s in various organisms have received little attention and no information is available for archaea. This study is aimed at addressing this research gap. Genome-wide analysis revealed 1204 P450s belonging to 34 P450 families and 112 P450 subfamilies, where some families and subfamilies are expanded in archaea. We also identified 353 ferredoxins belonging to the four types 2Fe-2S, 3Fe-4S, 7Fe-4S and 2[4Fe-4S] in 40 archaeal species. We found that bacteria and archaea shared the CYP109, CYP147 and CYP197 families, as well as several ferredoxin subtypes, and that these genes are co-present on archaeal plasmids and chromosomes, implying the plasmid-mediated lateral transfer of these genes from bacteria to archaea. The absence of ferredoxins and ferredoxin reductases in the P450 operons suggests that the lateral transfer of these genes is independent. We present different scenarios for the evolution and diversification of P450s and ferredoxins in archaea. Based on the phylogenetic analysis and high affinity to diverged P450s, we propose that archaeal P450s could have diverged from CYP109, CYP147 and CYP197. Based on this study’s results, we propose that all archaeal P450s are bacterial in origin and that the original archaea had no P450s.

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“…The [4Fe–4S] clusters are considered the first to have evolved ( Beinert et al, 1997 ; Meyer, 2008 ) and ferredoxins of this type are the most ubiquitous and abundantly present in anaerobic organisms, whereas [2Fe–2S] cluster-type ferredoxins are abundant in aerobic organisms ( Nzuza et al, 2021 ). The [3Fe−4S] cluster can be considered as a cubane [4Fe−4S] cluster missing one of the irons ( Campbell et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Structural insights into 3Fe–4S ferredoxins diversity in M. tuberculosis highlighted by a first redox complex with P450

Gilep

Varaksa²,

Bukhdruker³

et al. 2023

Front. Mol. Biosci.

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Ferredoxins are small iron–sulfur proteins and key players in essential metabolic pathways. Among all types, 3Fe–4S ferredoxins are less studied mostly due to anaerobic requirements. Their complexes with cytochrome P450 redox partners have not been structurally characterized. In the present work, we solved the structures of both 3Fe–4S ferredoxins from M. tuberculosis—Fdx alone and the fusion FdxE–CYP143. Our SPR analysis demonstrated a high-affinity binding of FdxE to CYP143. According to SAXS data, the same complex is present in solution. The structure reveals extended multipoint interactions and the shape/charge complementarity of redox partners. Furthermore, FdxE binding induced conformational changes in CYP143 as evident from the solved CYP143 structure alone. The comparison of FdxE–CYP143 and modeled Fdx–CYP51 complexes further revealed the specificity of ferredoxins. Our results illuminate the diversity of electron transfer complexes for the production of different secondary metabolites.

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Diversification of Ferredoxins across Living Organisms

Cited by 12 publications

References 69 publications

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species

Evolution of Cytochrome P450 Enzymes and Their Redox Partners in Archaea

Structural insights into 3Fe–4S ferredoxins diversity in M. tuberculosis highlighted by a first redox complex with P450

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