Biology subjects

Kim, S. B.

Publications and source records attributed to Kim, S. B..

5 recordsLinked to original sources

bioRxiv2026

Programmable domestication of thermophilic bacteria through removal of non-canonical defense systems

Thermophilic bacteria offer major advantages for industrial biotechnology, yet most remain genetically intractable because cellular defense systems block efficient DNA acquisition. Here, we present a programmable domestication strategy that converts wild Geobacillus strains into genetically tractable thermophilic hosts. We developed the Domestication of Non-Model Bacteria (DNMB) Suite, a multi- omics-guided computational framework that systematically identifies genetic barriers to transformation. DNMB analysis revealed that non-canonical nuclease-based defense systems, including Wadjet II, constitute dominant barriers to DNA uptake in previously intractable Geobacillus strains. Targeted deletion of these loci increased transformation efficiency by up to six orders of magnitude. We further established a hierarchical thermophilic engineering toolkit that integrates plasmid artificial modification, conjugation-assisted DNA delivery, and genome editing using an endogenous CRISPR-Cas9 system. The resulting domesticated strains support stable heterologous expression and tunable genetic control at elevated temperatures. Together, these results establish a generalizable framework for transforming genetically intractable thermophiles into programmable industrial chassis.

bioengineering↗

bioRxiv2026

Chemical activation of mitophagy via the N-degron pathway alleviates mitochondrial neuropathies

Pharmacological activation of mitophagy offers a promising strategy to eliminate dysfunctional mitochondria. We previously identified the autophagy receptor p62/SQSTM1 as an N-recognin whose activity is enhanced by Arg/N-degrons. Here, we show that Arg/N-degrons generated by ATE1-encoded R-transferase regulate p62-mediated mitophagy by promoting its recruitment to damaged mitochondria. Structural modification of Arg/N-degrons yielded ATB1071, a 443.5-Da orally bioavailable compound that activates p62 and induces stress-selective mitophagy through both Parkin-independent pathways involving NIPSNAP1 and NIPSNAP2, and a Parkin-dependent pathway involving the substrate EBP1/PA2G4. In Ndufs4-/- mice, a Leigh syndrome (LS) model, ATB1071 induced mitophagy in the brain and exerted therapeutic benefits by reducing neuroinflammation, improving muscle strength and neuromuscular coordination, and extending lifespan. In cerebral ischemia-reperfusion (IR) model mice, ATB1071 reduced infarct volume and neuronal death, and ameliorated multiple behavioral deficits through EBP1-dependent mitophagy. Pharmacokinetic (PK) and toxicological analyses support ATB1071 as a preclinical candidate for mitochondria-associated neurological injury.

cell biology↗

bioRxiv2025

Targeted degradation of pathologic tau aggregates via AUTOTAC ameliorates tauopathy

The pathogenesis of tauopathies including Alzheimers disease (AD) and progressive supranuclear palsy (PSP) involves the misfolding and aggregation of tau. Here, we employed AUTOTAC to induce the lysosomal degradation of intraneuronal tau aggregates. ATB2005A is a 734-Da chimera that simultaneously binds {beta}-sheet-rich tau aggregates and the autophagic receptor p62/SQSTM1, leading to autophagosomal sequestration and lysosomal co-degradation. In mouse models of tauopathies, orally administered ATB2005A lowered intraneuronal tau aggregates and exerted the therapeutic efficacy in neuroinflammation as well as cognition, behavior, and muscle movements. A Phase 2 clinical trial (U34401-4/2023/14) with companion dogs carrying canine cognitive dysfunction (CCD) demonstrated the efficacy of ATB2005A, as a veterinary medicine, to reverse the disease progression. ATB2005A is under Phase 1 clinical trial with human participants in Korea (202300697). These results validate AUTOTAC as a versatile platform for developing therapeutics to eradicate toxic protein aggregates in a wide range of proteinopathies.

neuroscience↗

bioRxiv2022

AIMP1-derived peptide secreted from hair follicle stem cells activates dermal papilla cells to promote hair growth

Hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) are crucial in the biogenesis and maintenance of hair follicles (HFs). In this study, a fragment derived from aminoacyl-tRNA synthetase-interacting multifunctional protein1 (AIMP1) was secreted from HFSCs to activate DPCs to maintain hair follicle homeostasis. A histological analysis revealed that AIMP1 levels in hair follicles decreased with hair loss. Hair regrowth in AIMP1-induced mice was faster than that in non-induced mice. Deletion mapping revealed 41 amino acids (TN41, aa 6-46) as the active region of AIMP1. The N-terminal peptide fragment of AIMP1 generated by MMP1 was secreted from Wnt-treated HFSCs to activate DPCs via FGFR2. TN41 activated Akt and ERK, increased {beta}-catenin, and enhanced DPCs activation. TN41 also promoted hair shaft elongation in cultured human hair follicles and improved the hair-inducing activity of cultured DPC spheroids. In summation, the AIMP1 fragment secreted from HFSCs appears to stimulate active hair regrowth through activating DPCs.

cell biology↗

bioRxiv2020

Hericerin derivatives from Hericium erinaceus exert BDNF-like neurotrophic activity in central hippocampal neurons and enhance memory

The traditional medicinal mushroom Hericium erinaceus has long been known for enhancing the peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. It was also reported to protect against ageing-dependent cognitive decline in wildtype and in Alzheimers disease mouse models suggesting a yet to be defined action on neurons of the central nervous system. Here, we purified and identified biologically active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom together with its hydrophobic derivative hericene A, were highly potent in inducing extensive axon outgrowth and neurite branching in the absence of serum demonstrating high neurotropic activity. NDPIH also induced enlarged growth cones suggestive of a brain-derived neurotrophic factor (BDNF)-like activity. Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA12 prevented NDPIH-induced neurotrophic activity providing evidence that NDPIH acts via TrkB receptors to mediate its neurotrophic effect in central neurons. Finally, in vivo treatment with H. erinaceus crude extract and hericene A significantly increased BDNF and downstream pathway and enhanced learning and memory in the novel object recognition memory test. Our results suggest that hericene A can promote BDNF-like activity in neurons in vitro and in vivo thereby enhancing recognition memory.

neuroscience↗