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5 recordsLinked to original sources
PubMed2026

Rapidly evolving aphid gall effector proteins exhibit saposin-like folds.

Many insects manipulate plants by injecting effector proteins. In one extreme example of this molecular "hijacking", Hormaphis cornu aphids inject bicycle proteins into Hamamelis virginiana (Witch Hazel), contributing to the development of novel organs called galls. Bicycle proteins share no amino acid sequence similarity with proteins of known function. Here, we report the crystal structures of two divergent bicycle proteins. Both proteins contain saposin-like folds: one with multiple disulfide bonds exhibits a helix swap; the other has no disulfide bonds and possesses two tandem domains. To explore the structural evolution of bicycle proteins, we predicted bicycle protein structures with Alphafold2 (AF2). While AF2 did not recover the two experimental structures using existing databases, it succeeded after we provided multiple sequence alignments (MSAs) containing protein sequences encoded in new genome sequences from closely related aphid species. Using this customized approach at scale, we generated 2400 high-confidence predictions for bicycle proteins from seven aphid species. This dataset revealed that bicycle proteins without cysteines are outliers in fold space and appear to have evolved from ancestral proteins with disulfide-bonded saposin-like folds. While all bicycle proteins contain predicted saposin-like folds, they display a vast diversity of structural and physicochemical properties. While this diversity thwarts prediction of conserved functions encoded in structure, it suggests that bicycle proteins have evolved to target diverse plant processes and/or to evade plant immune surveillance.

AlphaFold predictions↗
PubMed2026

Biogeographic patterns and metabolic potential of chemoautotrophic communities in cold seep sediments across subarctic to tropical regions.

Cold seeps are hotspots of chemoautotrophic primary production, yet how chemoautotrophic community structure and dark carbon fixation (DCF) vary across climatic regions remains unclear. We combined incubation experiments and metagenomics to compare chemoautotrophic communities in cold seep sediments across northwestern Pacific marginal seas, from the subarctic Okhotsk Sea to the tropical South China Sea. Incubation experiments demonstrated higher DCF rates in tropical (1.20 μg C g-1 day-1) than subarctic (0.35 μg C g-1 day-1) sediments (p = 0.002). Analyses of 133 cold seep sediment metagenomes (26 in this study and 107 from NCBI, spanning 0-240 cmbsf) revealed that subarctic chemoautotrophs were dominated by Chloroflexota, Asgardarchaeota, Campylobacterota, and Thermoproteota, whereas tropical chemoautotrophs were dominated by Pseudomonadota and Asgardarchaeota, with higher alpha diversity and integrated co-occurrence networks observed in tropical sediments. Representative genes of the Calvin-Benson-Bassham (CBB) cycle, the 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle, and the 3-hydroxypropionate (3HP) bicycle were enriched in tropical sediments, whereas reductive tricarboxylic acid (rTCA) cycle and Wood-Ljungdahl (WL) pathway genes predominated in subarctic sediments. Genome-resolved analysis showed that CBB cycle potential was concentrated in Pseudomonadota in tropical sediments and in Asgardarchaeota in subarctic sediments, and was most strongly correlated with nitrogen metabolism genes, whereas rTCA cycle potential was concentrated in Campylobacterota across both sediments, coupled strongly to sulfur metabolism. Depth profiling revealed surface communities dominated by Campylobacteria using rTCA cycle in subarctic sediments, and Alphaproteobacteria and Gammaproteobacteria using CBB cycle in tropical sediments, whereas the WL pathway predominated in Dehalococcoidia and Lokiarchaeia in the deeper layers of both regions. This study provides a comparative framework for chemoautotrophic biogeography across climatically distinct seeps.

Climate zones↗
PubMed1990

Microbial isopenicillin N synthase genes: structure, function, diversity and evolution.

Clinically and economically, penicillins and cephalosporins are the most important class of the beta-lactam antibiotics. They are produced by a wide variety of microorganisms including numerous species of Streptomyces, some unicellular bacteria and several filamentous fungi. A key step common to their biosynthetic pathways is the conversion of a linear, cysteine-containing tripeptide to a bicyclic beta-lactam antibiotic by isopenicillin N synthase. Recent successes in the cloning and expression of isopenicillin N synthase genes now permit production of a plentiful supply of this enzyme, which may be used for structural and mechanistic studies, or for biotechnological applications in the creation of novel beta-lactam compounds from peptide analogues. New ideas concerning the evolution and prevalence of the penicillin and cephalosporin biosynthetic genes have emerged from studies of isopenicillin N synthase genes.

Amino Acid Sequence↗
PubMed2025

Enzymatic Anti-Baldwin Ring-Closure Cascade for Fused Bicyclic Ether Formation.

Pyrenulic acids are cytotoxic polyketides isolated from the ascomycete Pyrenula sp. derived from Vietnamese lichen that are characterized by complex fused cyclic core structures. Genome sequencing, in silico sequence analysis, and RT-PCR studies identified the pyrenulic acid (pya) biosynthetic gene cluster. Based on a functional analysis of the enzymes by expression of each gene in a heterologous host using Aspergillus nidulans, we discovered two cytochrome P450s PyaJ and PyaG that effect epoxidation and hydroxylation of the alkyl chain terminal, respectively, and an α/β hydrolase PyaF that constructs a 6- and 7-membered fused bicyclic diether skeleton by catalyzing successive epoxide ring-opening 6-endo and 7-endo cyclization reactions. To elucidate the detailed mechanism of pyrenulic acid formation, we obtained PyaF as a recombinant enzyme and performed an in vitro experiment, which confirmed catalysis by PyaF of the cyclization reaction. In addition, we performed alignment analysis of PyaF with α/β hydrolases with known functions, as well as an in-depth computational study. In-depth computational analyses of the cyclization reaction pathways with density functional theory quantum mechanics and detailed characterization of PyaF by Chai-1-based protein structure modeling with molecular dynamics simulations and site-specific mutagenesis predicted the active amino acid residues of this serine α/β hydrolase to be an unusual catalytic serine tetrad involving Ser170, Asn342, Asp314, and His169, with Tyr255 and His284 acting as general bases to facilitate opening of the epoxides. Our study provides insight into how regioselectivity of enzymatic anti-Baldwin epoxide ring-opening cascades for the formation of a fused cyclic ether structure is controlled.

Cyclization↗
PubMed2026

Cytochrome P450- and Dehydrogenase-Mediated Regiospecific and Stereoselective Formation of β- and γ-Lactones in Drimane-Type Sesquiterpenoid Biosynthesis.

Lactone-containing natural products are important candidates for drug discovery. Drimane-type sesquiterpenes (DTSs), characterized by a bicyclic trans-decalin scaffold, can bear both β- and γ-lactone moieties. While γ-lactone-containing DTSs have frequently been reported, β-lactone-containing derivatives are rare, and their biosynthesis remains unexplored. Here, we identified a biosynthetic gene cluster (dri) in Aspergillus ustus and confirmed ustidrimane A (1), a β- and γ-lactone-containing DTS, as its product. Heterologous gene expression, precursor feeding, and enzymatic investigation provided evidence for the formation of both lactone rings. In both cases, the reaction cascade is initiated by regiospecific (and stereoselective) methyl hydroxylation, followed by regiospecific and stereoselective oxidation of one hydroxymethyl group to an aldehyde. The resulting hemiacetal was proven to be subsequently oxidized to a lactone. The β-lactone formation is catalyzed by two cytochrome P450 enzymes (DriE and DriF), followed by two oxidation steps catalyzed by two dehydrogenases (DriG and DriH). These findings differ entirely from the known β-lactone formation in fatty acid-, PKS-, and NRPS-derived metabolites. The subsequent γ-lactone formation is catalyzed by a P450 (DriJ) and a dehydrogenase (DriD). DriJ has been shown to be involved in both methyl hydroxylation and hemiacetal formation, while DriD is responsible for the hemiacetal oxidation and also contributes moderately to its formation. Collectively, these findings establish a sequential P450/dehydrogenase-mediated oxidative cascade for the construction of two distinct lactone motifs within a single DTS scaffold. Moreover, they provide the first insight into the β-lactone formation in terpenes, thus unveiling a new strategy for the construction of this structural motif.

Lactones↗