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Microbes & Immunity Identifying hydrogenase orthologs in the human proteome

classical hydrogenase activity due to the absence of a Consent for publication
functional Ni-Fe di-metal core. A detailed analysis of
protein sequences reveals stronger similarities between the Not applicable.
human proteins NDUFS2 and NDUFS7 – key components Availability of data
of the ubiquinone binding channel in complex I – and
their homologous proteins in the Ca. Heimdallarchaeota, The data supporting the findings of this study are available
with hydrogenase similarity percentages of 27% and from the corresponding author on request.
35%, respectively. In contrast, similarities with the References
α-proteobacterium R. sphaeroides are less than 20%, and
those with the δ-proteobacterium D. carbinolicus are 23% 1. Campbell C, Kandalgaonkar MR, Golonka RM, Yeoh BS,
and 35%. These findings suggest a potential evolutionary Vijay-Kumar M, Saha P. Crosstalk between gut microbiota
link between archaeal hydrogenases and complex I and host immunity: Impact on inflammation and
38
immunotherapy. Biomedicines. 2023;11(2):294.
subunits, although further research is necessary to confirm
this hypothesis. doi: 10.3390/biomedicines11020294
Of particular relevance to microbial and immunological 2. Mann ER, Lam Y K, Uhlig HH. Short-chain fatty acids:
research, this study identifies two motifs within the Linking diet, the microbiome and immunity. Nat Revs
Immunol. 2024;24:577-595.
NDUFS7 subunit – the PKC phosphorylation site
(-RASPRQS-) and the N-myristoylation site (-IPGCPP-) doi: 10.1038/s41577-024-01014-8
– as potential sites for H activity. If H is found to 3. Kim CH. Complex regulatory effects of gut microbial short-
2
2
support the structure and function of these motifs, it chain fatty acids on immune tolerance and autoimmunity.
could mitigate electron leakage, reduce the formation Cell Mol Immunol. 2023;20(4):341-350.
of ROS, and prevent oxidative damage. Such outcomes doi: 10.1038/s41423-023-00987-1
would have significant implications for maintaining 4. Checa J, Aran JM. Reactive oxygen species: Drivers of
redox balance and limiting pro-inflammatory signaling, physiological and pathological processes. J Inflamm Res.
thereby highlighting a promising therapeutic avenue for 2020;13:1057-1073.
regulating immune responses and microbial interactions doi: 10.2147/JIR.S275595
in human cells.
5. Ohta S. Molecular hydrogen may activate the transcription
Acknowledgments factor Nrf2 to alleviate oxidative stress through the hydrogen-
targeted porphyrin. Aging Pathobiol Ther. 2023;5(1):25-32.
The author would like to thank Professor J. T. Hancock for
the insightful discussions that led to the conception of this doi: 10.31491/APT.2023.03.104
research. 6. Shim JA, Ryu JH, Jo Y, Hong C. The role of gut microbiota in
T cell immunity and immune mediated disorders. Int J Biol
Funding Sci. 2023;19(4):1178-1191.
This research was co-funded by Water Fuel Engineering doi: 10.7150/ijbs.79430
and the University of the West of England. Funding 7. Wolf PG, Biswas A, Morales SE, Greening C, Gaskins HR.
identification number 7096050. Project code: RDAS0184. H2 metabolism is widespread and diverse among human
colonic microbes. Gut Microbes. 2016;7(3):235-245.
Conflict of interest
doi: 10.1080/19490976.2016.1182288
This work was part-funded by Water Fuel Engineering, a 8. Campbell A, Gdanetz K, Schmidt AW, Schmidt TM. H2
manufacturer of oxy-hydrogen inhalation devices. Grace generated by fermentation in the human gut microbiome
Russell is the Guest Editor of this special issue but was not influences metabolism and competitive fitness of gut
involved in the editorial or peer-review processes for this butyrate producers. Microbiome. 2023;11(1):133.
paper, either directly or indirectly. doi: 10.1186/s40168-023-01565-3

Author contributions 9. Sharma P, Parakh SK, Tsui TH, et al. Synergetic anaerobic
digestion of food waste for enhanced production of
This is a single-authored manuscript. biogas and value-added products: Strategies, challenges,
and techno-economic analysis. Crit Rev Biotechnol.
Ethics approval and consent to participate 2024;44(6):1040-1060.
Not applicable. doi: 10.1080/07388551.2023.2241112

Volume 1 Issue 2 (2024) 89 doi: 10.36922/mi.4544