L-Homoserine is a non-proteinogenic amino acid precursor for value-added chemicals. We developed a new producing strain via rational re-engineering and tolerance evolution, constructing a non-auxotrophic, plasmid-free chassis from HS15 using dynamic regulation and 5′-untranslated optimization. A mutator system accelerated evolution, enhancing tolerance. Strain NS18 achieved 144.5 g/L titer, 0.48 g/g yield, and 3.01 g/L/h productivity in minimal salt medium, which are the highest reported. Multi-omics revealed redox mechanisms and upregulated branched-chain amino acids for adaptation.

Tuberculosis granulomas are immune cell aggregates formed during Mycobacterium tuberculosis infection. However, the immunological features and regulatory mechanisms in granulomas remain unclear. Prof. LIU’s group and collaborators employ spatial transcriptomics to map locations, transcriptomes, and interactions of macrophages and T cells in granulomas, uncovering their immune plasticity shaped by lesion severity and proximity to multinucleated giant cells or tertiary lymphoid structures. They further identify a lysosomal cholesterol overload-impaired innate-adaptive immune axis in granulomas, proposing a cholesterol-targeting strategy against tuberculosis.

Broad-spectrum host restriction factors against bacteria and viruses remain largely unclear. Prof. LIU’s group and collaborators identify the small GTPase Rab14 as such a restriction factor, which inhibits CAMK2D-catalyzed V0a1 phosphorylation to elicit V0a1 interaction with the COPⅡ complex, followed by promoting V-ATPase trafficking from the endoplasmic reticulum to lysosomes for promoting lysosomal acidification and pathogen clearance. These findings demonstrate an unrecognized intrinsic immune mechanism mediated by Rab14-CAMK2D-V-ATPase axis, which might be a promising target for infectious diseases.

Fungal secondary metabolism is critical for pathogen-host interactions, but its regulatory link to virulence is unclear. This study identifies an A. fumigatus CsdA-LaeB regulatory hub that controls fumiquinazoline C (FqC) biosynthesis; FqC mediates virulence, with CsdA/LaeB expression inversely correlating with FqC in clinical isolates, providing new post-transcriptional regulation insights and therapeutic strategies for invasive fungal diseases.

The evolution and domestication of mushrooms remains poorly understood. Prof. ZHAO Rui-Lin’s lab revealed that divergence and gene flow driven by Quaternary glacial cycles lead to the current mixed origins of A. bisporus populations. Moreover, the white-cap trait is the key artificial selected trait, and AbPPO1 was identified as a key gene for cap-color variation.