By Mike Gilman, serial entrepreneur and veteran biotech executive, as part of the From The Trenches feature of LifeSciVC My thesis advisor, Mike Chamberlin, passed away last week. I owe much of who I ...

Nature Structural & Molecular Biology, Published online: 11 November 2025; doi:10.1038/s41594-025-01719-xAlphaSync synchronizes AlphaFold Protein Structure Database predictions with UniProt sequences, providing up-to-date protein structures with residue-level annotations for humans, model organisms and pathogens through an accessible web interface and application programming interface.

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Abstract. Polyethylene terephthalate (PET)-hydrolyzing enzymes (PETases) are a recently discovered enzyme class capable of plastic degradation. PETases are

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Eukaryotic intracellular compartmentalization is a key innovation in the evolution of complex cellular life. While microcompartments enable metabolic specialization in many bacteria, to our knowledge, no analogous systems have been identified in Archaea. Here, we report the discovery of archaeal microcompartments (AMCs) in Hodarchaeales, an order within the phylum Promethearchaeati (Asgard archaea) that includes the closest known archaeal relatives of eukaryotes. Phylogenetic and structural analyses indicate that these catabolic AMCs, which are specialized for sugar-phosphate metabolism, were acquired by horizontal gene transfer from deep-rooted bacteria of the phylum Myxococcota. The shell pentamers of AMCs are fused to lysine/arginine-rich intrinsically disordered regions that capture cytosolic DNA, facilitating nutrient scavenging. Reaction-diffusion modelling predicted that enzyme colocalization and substrate channelling within AMCs, can drive an approximately 100-fold increase in NADH flux. Thus, the AMCs substantially boost energy production in the cell and might have primed the archaeal host for eukaryogenesis. ### Competing Interest Statement The authors have declared no competing interest. National Natural Science Foundation of China, 32370055, 32393970, 32225003, 32200099, 92051102 Shenzhen Natural Science Foundation, JCYJ20230808105711023 Guangdong Basic and Applied Basic Research, 2025A1515012817 Project of Department of Education of Guangdong Province, 2025KCXTD039 Shenzhen University 2035 Program for Excellent Research, 2022B002 Synthetic Biology Research Center of Shenzhen University Moore–Simons Project on the Origin of the Eukaryotic Cell Simons and Moore Foundation, 73592LPI Simons Foundation Investigator in Aquatic Microbial Ecology Award, LI-SIAME-00002001 Intramural Research Program of the National Institutes of Health of the USA

The ongoing evolutionary arm race between archaea and their viruses has led to the development of diverse defense systems against viruses. While recent computational approaches have uncovered many bacterial antiviral defense systems, the viral infection strategies and antiviral responses of archaea remain poorly explored. In this study, we identified antiviral defense systems encoded in the genomes of 20 recently sequenced haloarchaeal strains. These systems are representative of the broader repertoire of defense systems present across all 253 complete sequenced Halobacteria (class) genomes in the RefSeq database. Detailed analysis showed that these haloarchaea usually harbor multiple different defense systems, with a particularly high abundance of uncharacterized predicted defense systems against viruses (Phage Defense Candidates (PDCs)). To further explore the impact of anti-viral defense mechanisms on host range, an extensive virus-host pair screening was performed using a panel of known virulent viruses. By correlating the genomic defense profiles with observed viral infectivity and adsorption profiles, a weak correlation between the number of encoded defense systems and viral susceptibility was detected. Specifically, hosts infected by fewer viruses tended to encode a broader repertoire of antiviral defense systems, whereas those with fewer defense systems were frequently infected. It was found that the host range of haloarchaeal viruses is majorly determined by the availability of viral receptors, whereas the presence of anti-viral defense systems plays a smaller but significant role. These findings offer valuable insights into the evolutionary pressure shaping archaeal antiviral strategies and lay the groundwork for future functional studies of archaeal defense systems.

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Natural genetic code expansion is a phenomenon wherein an additional amino acid is encoded by a stop codon. These nonstandard amino acids are benef...