bims-vitmet 2025-08-31 papers

Issue of 2025–08–31
three papers selected by
Onurkan Karabulut, Berkeley City College

Genes Dev. 2025 Aug 22.

Multifaceted role of the vitamin B6 pathway in cancer: metabolism, immune interaction, and temporal and spatial regulation.

Sushanta Kumar Mishra, Bo Li, Ana S H Costa, Linda Van Aelst, Lingbo Zhang.

Vitamin B6 is a metabolic cofactor that underpins critical regulatory pathways, including amino acid flux, one-carbon pathways, redox homeostasis, and neurotransmitter biosynthesis. Emerging evidence suggests that vitamin B6 deficiency or its metabolic dysregulation perturbs these core metabolic pathways, driving oncogenic programs in both solid tumors and hematologic malignancies. Moreover, vitamin B6-dependent processes can modulate several tumorigenic processes, such as proliferation, oncogenic signaling, immune regulation, and adaptive metabolic reprogramming. The tumor-specific spatiotemporal dynamics of vitamin B6 metabolism uncover context-dependent metabolic vulnerabilities that are tightly regulated by cellular state and tumor niche. This review addresses emerging mechanistic insights into the multifaceted functions of vitamin B6 in tumorigenesis. Furthermore, it proposes dynamic vitamin B6 metabolism as a promising therapeutic axis, offering novel opportunities for tumor-specific targeted intervention.

Keywords: cancer; immune regulation; metabolism; temporal and spatial specificity; vitamin B6

DOI: https://doi.org/10.1101/gad.352770.125

Int J Mol Sci. 2025 Aug 09. pii: 7703. [Epub ahead of print]26(16):

A Comprehensive Review of Fortification, Bioavailability, and Health Benefits of Folate.

Jiarun Li, Hanying Duan, Hosahalli Ramaswamy, Chao Wang.

Folate is an essential vitamin involved in one-carbon metabolism. It can be acquired from many food sources or in synthetic form. A wide range of processing methods have been studied to improve the bioaccessibility and bioavailability of folate in foods, yet this is often accompanied by a decrease in stability. Encapsulation technology has emerged as an effective solution for protecting folate from degradation and liberation while also improving its bioavailability. Folate deficiency is a prevalent phenomenon worldwide, particularly in underprivileged countries, leading to various health problems, such as neural tube defects. Thus, folate was fortified through both exogenous addition and biofortification. Gene editing technology, especially CRISPR-Cas9, has great promise in this field when compared to transgenic engineering, because transgenic engineering may pose safety concerns and environmental risks. While ongoing research has identified additional potential effects of folate, the dosage and duration remain important factors to consider for optimal health outcomes. The mechanisms of how folate promotes the production of neurotransmitters associated with the gut microbiota-brain axis and reduces depression are not well understood. In addition to folate alone, there may be synergistic effects of combined supplementation of folate and other nutrients or medications, but this is not yet fully clarified and requires further examination. This review summarizes the food sources, enrichment, bioaccessibility, and bioavailability of folate. Furthermore, the health benefits of folate, including neural tube protection, cardiovascular protection, neuroprotection, anti-cancer, immune response augmentation, and gut homeostasis maintenance, with their potential bioactivity mechanisms, are discussed.

Keywords: anti-inflammatory; antioxidant; bioaccessibility; folate; folate enrichment; health benefits; homocysteine

DOI: https://doi.org/10.3390/ijms26167703

Adv Microb Physiol. 2025 ;pii: S0065-2911(25)00019-0. [Epub ahead of print]87 257-298

Engineering biology and chemical approaches to the construction of vitamin B12 analogues and antivitamins B12 as probes and therapeutic agents.

Michael D Paxhia, Freya L Hartshorn, Evelyne Deery, Bernhard Kräutler, Martin J Warren.

Vitamins are indispensable cofactors that expand the chemical capabilities of enzymes beyond the inherent limitations of amino acid side chains. Among them, vitamin B₁₂ is particularly remarkable due to its exceptional structural complexity, the presence of a cobalt-centered corrin ring, and its exclusive biosynthetic origin in prokaryotes. This review explores the biosynthesis, transport, and biological significance of B₁₂, with an emphasis on the growing toolbox of synthetic analogues designed for research and therapeutic use. Recent advances in synthetic biology have enabled the complete heterologous expression of the aerobic B12 biosynthesis pathway in Escherichia coli, facilitating the high-yield production of biosynthetic intermediates and cobalt-free B12-precursors. These intermediates serve as platforms for the generation of metbalamins, metal-substituted cobalamin analogues incorporating rhodium, nickel, zinc, and other transition metals. In parallel, novel organo-antimetabolites and fluorescently labelled derivatives have been developed to probe B₁₂-dependent enzymes, trace vitamin transport in living systems, and selectively disrupt microbial or disease-linked metabolism. These synthetic analogues function as versatile tools for imaging, mechanistic dissection, and metabolic inhibition and more specifically in the case of molecules that counteract the physiological effects of vitamin B12 in animal systems hold potential as antivitamins B12. Collectively, they offer powerful new approaches to study nutrient trafficking, engineer cofactor interactions, and develop targeted antimicrobial or anticancer strategies. The review concludes by discussing future directions in applying engineering biology and chemical synthesis to further diversify and exploit the functional potential of the cobalamin scaffold.

Keywords: Antivitamins b(12); Biosynthesis; Cobalamin; Corrin; Engineering biology; Metbalamin; Synthetic biology; Tetrapyrrole; Transition metals; Vitamin B(12)

DOI: https://doi.org/10.1016/bs.ampbs.2025.07.003