Song, H. J. | bioRxiv Science

bioRxiv2026

Who Formed All That Iron?: A Novel Antarctic Chemolithotroph Drives Iron Biomineralization

Iron mineralization has profoundly influenced Earths biogeochemical history1,2, yet the specific mechanisms underlying banded iron formation (BIF) remain unresolved3-5. Here we profile the microbiomes of Holocene sediments beneath the Larsen C Ice Shelf (LCIS), Antarctica6-8, through stratigraphic analysis of sedimentary ancient DNA combined with metagenomics. Distinct microbial phases aligned with glacial facies boundaries, with sub-ice shelf communities dominated by chemolithoautotrophs including an uncultured Thermodesulfovibrionia. This bacterium, visualized by fluorescence in situ hybridization and designated Candidatus Mariimomonas ferrooxydans (phylum Nitrospirota), emerged as a keystone taxon with high network centrality. Its genome encodes Cyc2, a fused porin-cytochrome outer membrane protein implicated in Fe(II) oxidation. Heterologous expression of Cyc2 in Escherichia coli confirmed its ability to catalyze iron oxidation, supporting iron precipitation under dark, anoxic conditions. These pristine LCIS sediments, unaltered since the last glacial maximum, provide a modern analogue for synglacial BIFs deposited during Neoproterozoic Snowball Earth events. Our findings deliver direct genomic and functional evidence for chemolithotrophic iron oxidation, challenge phototroph-centric models of BIF genesis, and highlight microbial iron cycling as a recurring force in Earths geochemical evolution. Beyond Earth, these insights inform interpretations of iron deposits on other planetary bodies.

microbiology↗

bioRxiv2020

KDS2010, a newly developed reversible MAO-B inhibitor, as an effective therapeutic candidate for Parkinson's disease

Background and PurposeMonoamine oxidase-B (MAO-B) is a long-standing therapeutic target for Parkinsons disease (PD), however, previous clinical studies demonstrated discouraging effects of currently available irreversible MAO-B inhibitors. Since KDS2010, a novel, potent, selective, and reversible MAO-B inhibitor, has been developed, here we tested its therapeutic potential in animal models of PD. Experimental ApproachWe designed and synthesized -aminoamide derivatives and compared the specificity to MAO-B and reversibility of each compound with KDS2010. To investigate the in vivo therapeutic effect, we used MPTP mouse model with two different regimes of 3-day administration (pre-treatment or post-treatment) and 30-day administration. We assessed the therapeutic potential using behavioral and immunohistochemical analyses. Additionally, the functional recovery by KDS2010 was tested in 6-hydroxydopamine-induced and A53T-alpha-synuclein overexpression models. Lastly, to validate the potential as a clinical drug candidate, we investigated the pharmacokinetics and toxicity of KDS2010 in non-human primates. Key ResultsKDS2010 showed the highest potency, specificity, and reversibility among the -aminoamide derivatives, with high bioavailability (>100%) and BBB permeability. KDS2010 also showed significant neuroprotective and anti-neuroinflammatory effects in the nigrostriatal pathway, leading to an alleviation of MPTP-induced parkinsonism in all administration regimes. In particular, the therapeutic effect of KDS2010 was superior to selegiline, an irreversible MAO-B inhibitor. KDS2010 also showed a potent therapeutic effect in 6-hydroxydopamine and A53T models. Moreover, KDS2010 showed virtually no toxicity or side-effect in non-human primates. Conclusion and ImplicationsKDS2010 shows excellent therapeutic potential and safety in various PD animal models. KDS2010, therefore, could be a next-generation therapeutic candidate for PD. Representative Schematic O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY What is already knownKDS2010 is a recently developed potent, selective, and reversible MAO-B inhibitor. MAO-B is critical for PD pathology through astrocytic GABA and H2O2 synthesis. What this study addsKDS2010 treatment dramatically recovers from PD-related pathology and motor deficit after pre- and post-treatment regimes in several animal models of PD. KDS2010 exhibits low toxicity and excellent pharmacokinetic profile in non-human primates. What is the clinical significance?KDS2010 is a safe and promising therapeutic candidate for Parkinsons disease. Reversible MAO-B inhibitors could be more effective for treatment of Parkinsons disease, overcoming the short-lived actions of irreversible MAO-B inhibitors.

pharmacology and toxicology↗