Multi-Omics Maps Medicinal Mushroom
The medicinal mushroom Ganoderma lingzhi produces its health-promoting ganoderic acids (GAs) in a tightly regulated spatial and temporal pattern, according to new research. Using an integrated multi-omics approach, researchers from Northeast Forestry University, China, and collaborators have, for the first time, mapped GA distribution across development stages and uncovered a key biosynthetic enzyme.
High-resolution MALDI-MSI analysis revealed that GAs concentrate in the mushroom’s outer shell – likely serving as a defense mechanism – and show stage-specific accumulation patterns, with 24 distinct GAs grouped into eight molecular weight clusters. To probe the genetic underpinnings, the team assembled complete telomere-to-telomere (T2T) genomes of two haploid strains and generated a single-cell transcriptomic atlas of the fruiting body, identifying six cell types and tracking shell development.
Integration of metabolomic and transcriptomic data identified a previously uncharacterized cytochrome P450 enzyme, GlCYP512A3, which catalyzes a late-stage oxidation in GA biosynthesis. This finding helps clarify downstream diversification steps that had remained elusive.
The study establishes a comprehensive framework for understanding and engineering GA biosynthesis, paving the way for optimized cultivation and therapeutic exploitation of G. lingzhi.
PHGDH Reprograms Macrophages in the Breast Cancer Microenvironment
PHGDH, a metabolic enzyme best known for its role in serine synthesis, has been found to play an unexpected second job: reprogramming macrophages within the breast cancer microenvironment. Rather than functioning solely in metabolism, PHGDH translocated to the nucleus of immune cells, where it suppressed transcription of the glutamine metabolism genes GLUD1 and GLS2. This action curbed tumor-supportive M2-like polarization and encouraged anti-tumor M1-like states.
The study, led by researchers at Sun Yat-sen University and Zhejiang Cancer Hospital, showed that PHGDH loss correlated with heightened expression of immune checkpoint molecules such as PD-L1 and promoted tumor progression. Conversely, restoring PHGDH or inhibiting downstream targets such as STAT3 reversed immunosuppressive traits in both human and mouse macrophages.
“PHGDH acts like a molecular switch,” commented senior author Zhenkun Na. “Its nuclear function in macrophages directly suppresses genes that would otherwise support tumor-promoting phenotypes.” The team’s findings suggest PHGDH could serve as both a therapeutic target and a biomarker for immunomodulation in breast cancer.
Ancient Enamel Preserves 18-Million-Year-Old Proteins
Researchers have retrieved protein fragments from 18-million-year-old fossilized teeth in Kenya’s Rift Valley, dramatically extending the known age of preserved peptides and opening new molecular avenues for studying extinct mammals. Led by scientists at Harvard University and the Smithsonian Museum Conservation Institute, the study used advanced liquid chromatography tandem mass spectrometry (LC-MS/MS) to uncover a surprisingly diverse proteome from ancient enamel.
Teeth – described by lead author Daniel Green as “rocks in our mouths” – are ideal for such work due to their hardness and mineral density. Targeting thick-enamel herbivores like early elephants and rhinoceroses, the team recovered peptide fragments involved in structural, metabolic, and transport functions – some dating back 18 million years. This extends the previous proteomic age record of 3.5 million years by some.
The researchers credited their success to improvements in LC-MS/MS and the natural durability of mature enamel, which protects against chemical and enzymatic degradation. Beyond tracing evolutionary relationships, the proteins may offer insight into extinct animals’ physiology, diets, and health.
As coauthor Emmanuel Ndiema noted, the findings let scientists “go beyond bones and morphology to reconstruct the molecular and physiological traits of extinct animals.”
Straight Outta Mars
A newly classified Martian meteorite, Northwest Africa (NWA) 16254, is shedding light on volcanic activity deep within Mars’ crust and mantle. Reported in Planet, the study revealed that this coarse-grained gabbroic shergottite crystallized in two distinct stages: first under high pressure at the mantle-crust boundary, then at shallower depths as magma ascended and cooled.
NWA 16254’s chemical profile includes low light rare earth elements (LREEs) and a reduced oxygen fugacity. Together, these traits suggest the meteorite formed from a long-lived, chemically depleted mantle reservoir – similar to the rare QUE 94201 meteorite.
To probe its composition, the team used TESCAN Integrated Mineral Analyzer (TIMA) imaging and LA-ICP-MS to map mineral phases and trace element distributions. Pyroxene zoning and titanium-bearing ilmenite revealed evidence of prolonged cooling under reducing conditions.
The findings challenge existing models of Martian volcanism by underscoring mantle heterogeneity and raising new questions about the planet’s redox evolution. Further isotopic dating could determine whether NWA 16254 records ancient magmatism or more recent thermal events, offering fresh insights into Mars’ deep geological history.
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