Li, Y.-x. | Search bioRxiv

bioRxiv2026

The recovery of 12,789 genomes revealed the diversity, function, and microbial interactions of the geothermal spring microbiome

Geothermal springs, characterized by extreme physicochemical conditions, represent ecologically and evolutionarily significant habitats that foster unique microbial communities and drive adaptive evolutionary processes. Despite their importance, the complex microbial interactions and underlying mechanisms governing community assembly in these environments remain poorly understood. In this study, we conducted systematic sampling across 49 geothermal springs in Tengchong, Yunnan, over a six-year period (2016-2021), and performed metagenomic sequencing on 152 samples. We successfully reconstructed 12,789 non-redundant microbial genomes, revealing an exceptionally high level of phylogenetic and functional diversity within the spring microbiomes. Our analyses demonstrate that pH and temperature are the primary deterministic drivers shaping both microbial species composition and functional potential, thereby segregating the communities into three distinct groups: acidic, hyperthermal, and thermal. Furthermore, ecological network analysis revealed that extreme environmental conditions significantly alter network topology, resulting in less complex but more efficient microbial interaction networks. Collectively, this study provides a comprehensive resource and mechanistic insights into the microbial diversity, community structure, and species interactions in geothermal spring ecosystems.

microbiology↗

bioRxiv2024

P450-Catalyzed Biaryl Macrocyclization of Leaderless Ribosomal Peptides

Macrocyclic peptides containing biaryl motifs, predominantly derived from natural products, are valuable scaffolds due to their structural rigidity and potent bioactivity. However, current synthetic methods remain constrained by the absence of broadly applicable strategies across chemocatalytic and biocatalytic platforms. Here, we discover a versatile P450 enzyme, GpeC, capable of facilitating oxidative C-C/O/N cross-coupling for peptide biaryl macrocyclization (PBC) with leader-independent activity. Crystal structure analysis of GpeC rationalizes leader-independent property and reveals adaptive recognition that enables access to diverse biaryl-linked macrocycles. GpeC exhibits exceptional substrate promiscuity, accommodating 19 of 20 canonical amino acids and diverse noncanonical analogs within a minimal tetrapeptide scaffold. The efficient semi-synthesis of the natural product Rubrin further demonstrated the versatility of GpeC. We further introduced lytic to tetraregion (LTT), a one-step, single enzyme synthesis for modular synthesis of biaryl-cyclized tetrapeptide. Overall, GpeCs robustness and programmability position it as a broadly applicable biocatalyst for the synthesis of biaryl macrocyclic peptides.

biochemistry↗

bioRxiv2022

Metagenomic discovery of Candidatus Parvarchaeales related lineages sheds light on the adaptation and diversification from neutral-thermal to acidic-mesothermal environments

Candidatus Parvarchaeales, representing a DPANN archaeal group with limited metabolic potentials and reliance on hosts for their growth, were initially found in acid mine drainage (AMD). Due to the lack of representatives, however, their ecological roles and adaptation to extreme habitats such as AMD, as well as how they diverge across the lineage remain largely unexplored. By applying genome-resolved metagenomics, 28 Parvarchaeales-associated metagenome-assembled genomes (MAGs) representing two orders and five genera were recovered. Among them, we identified three new genera and proposed the names Candidatus Jingweiarchaeum, Candidatus Haiyanarchaeum, and Candidatus Rehaiarchaeum with the former two belonging to a new order Candidatus Jingweiarchaeales. Further analyses of metabolic potentials revealed substantial niche differentiation between Jingweiarchaeales and Parvarchaeales. Jingweiarchaeales may rely on fermentation, salvage pathways, partial glycolysis, and pentose phosphate pathway (PPP) for energy reservation, while the metabolic potentials of Parvarchaeales might be more versatile. Comparative genomic analyses suggested that Jingweiarchaeales are more favorable to habitats with higher temperatures and Parvarchaeales are better adapted to acidic environments. We further revealed that the thermal adaptation of these lineages especially for Haiyanarchaeum might rely on innate genomic features such as the usage of specific amino acids, genome streamlining, and hyperthermal featured genes such as rgy. Notably, the acidic adaptation of Parvarchaeales was possibly driven by horizontal gene transfer (HGT). Reconstruction of ancestral states demonstrated that both may originate from thermal and neutral environments and later spread to mesothermal and acidic environments. These evolutionary processes may also be accompanied by adaptation toward oxygen-rich environments via HGT. ImportanceCandidatus Parvarchaeales may represent a lineage uniquely distributed in extreme environments such as AMD and hot springs. However, little is known about the strategies and processes of how they adapted to these extreme environments. By the discovery of potential new order-level lineages - Jingweiarchaeales and in-depth comparative genomic analysis, we unveiled the functional differentiation of these lineages. Further, we show that the adaptation to high-temperature and acidic environments of these lineages was driven by different strategies, with the prior relying more on innate genomic characteristics and the latter more on the acquisition of genes associated with acid tolerance. Finally, by reconstruction of ancestral states of OGT and pI, we showed the potential evolutionary process of Parvarchaeales-related lineages with regard to the shift from a high-temperature environment of their common ancestors to low-temperature (potentially acidic) environments.

microbiology↗