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1. dbCAN3: automated carbohydrate-active enzyme and substrate annotation

   https://doi.org/10.1093/nar/gkad328  

   Zheng, Jinfang ; Ge, Qiwei ; Yan, Yuchen ; Zhang, Xinpeng ; Huang, Le ; Yin, Yanbin ( May 2023 , Nucleic Acids Research)

   Carbohydrate active enzymes (CAZymes) are made by various organisms for complex carbohydrate metabolism. Genome mining of CAZymes has become a routine data analysis in (meta-)genome projects, owing to the importance of CAZymes in bioenergy, microbiome, nutrition, agriculture, and global carbon recycling. In 2012, dbCAN was provided as an online web server for automated CAZyme annotation. dbCAN2 (https://bcb.unl.edu/dbCAN2) was further developed in 2018 as a meta server to combine multiple tools for improved CAZyme annotation. dbCAN2 also included CGC-Finder, a tool for identifying CAZyme gene clusters (CGCs) in (meta-)genomes. We have updated the meta server to dbCAN3 with the following new functions and components: (i) dbCAN-sub as a profile Hidden Markov Model database (HMMdb) for substrate prediction at the CAZyme subfamily level; (ii) searching against experimentally characterized polysaccharide utilization loci (PULs) with known glycan substates of the dbCAN-PUL database for substrate prediction at the CGC level; (iii) a majority voting method to consider all CAZymes with substrate predicted from dbCAN-sub for substrate prediction at the CGC level; (iv) improved data browsing and visualization of substrate prediction results on the website. In summary, dbCAN3 not only inherits all the functions of dbCAN2, but also integrates three new methods for glycan substrate prediction.

    

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2. dbCAN-seq update: CAZyme gene clusters and substrates in microbiomes

   https://doi.org/10.1093/nar/gkac1068  

   Zheng, Jinfang ; Hu, Boyang ; Zhang, Xinpeng ; Ge, Qiwei ; Yan, Yuchen ; Akresi, Jerry ; Piyush, Ved ; Huang, Le ; Yin, Yanbin ( November 2022 , Nucleic Acids Research)

   Carbohydrate Active EnZymes (CAZymes) are significantly important for microbial communities to thrive in carbohydrate rich environments such as animal guts, agricultural soils, forest floors, and ocean sediments. Since 2017, microbiome sequencing and assembly have produced numerous metagenome assembled genomes (MAGs). We have updated our dbCAN-seq database (https://bcb.unl.edu/dbCAN_seq) to include the following new data and features: (i) ∼498 000 CAZymes and ∼169 000 CAZyme gene clusters (CGCs) from 9421 MAGs of four ecological (human gut, human oral, cow rumen, and marine) environments; (ii) Glycan substrates for 41 447 (24.54%) CGCs inferred by two novel approaches (dbCAN-PUL homology search and eCAMI subfamily majority voting) (the two approaches agreed on 4183 CGCs for substrate assignments); (iii) A redesigned CGC page to include the graphical display of CGC gene compositions, the alignment of query CGC and subject PUL (polysaccharide utilization loci) of dbCAN-PUL, and the eCAMI subfamily table to support the predicted substrates; (iv) A statistics page to organize all the data for easy CGC access according to substrates and taxonomic phyla; and (v) A batch download page. In summary, this updated dbCAN-seq database highlights glycan substrates predicted for CGCs from microbiomes. Future work will implement the substrate prediction function in our dbCAN2 web server.

    

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3. Cultivable, Host-Specific Bacteroidetes Symbionts Exhibit Diverse Polysaccharolytic Strategies

   https://doi.org/10.1128/AEM.00091-20  

   Vera-Ponce de León, Arturo ; Jahnes, Benjamin C. ; Duan, Jun ; Camuy-Vélez, Lennel A. ; Sabree, Zakee L. ( April 2020 , Applied and Environmental Microbiology)

   Drake, Harold L. (Ed.)

   ABSTRACT Beneficial gut microbes can facilitate insect growth on diverse diets. The omnivorous American cockroach, Periplaneta americana (Insecta: Blattodea), thrives on a diet rich in plant polysaccharides and harbors a species-rich gut microbiota responsive to host diet. Bacteroidetes are among the most abundant taxa in P. americana and other cockroaches, based on cultivation-independent gut community profiling, and these potentially polysaccharolytic bacteria may contribute to host diet processing. Eleven Bacteroidetes isolates were cultivated from P. americana digestive tracts, and phylogenomic analyses suggest that they were new Bacteroides , Dysgonomonas , Paludibacter , and Parabacteroides species distinct from those previously isolated from other insects, humans, and environmental sources. In addition, complete genomes were generated for each isolate, and polysaccharide utilization loci (PULs) and several non-PUL-associated carbohydrate-active enzyme (CAZyme)-coding genes that putatively target starch, pectin, and/or cellulose were annotated in each of the isolate genomes. Type IX secretion system (T9SS)- and CAZyme-coding genes tagged with the corresponding T9SS recognition and export C-terminal domain were observed in some isolates, suggesting that these CAZymes were deployed via non-PUL outer membrane translocons. Additionally, single-substrate growth and enzymatic assays confirmed genomic predictions that a subset of the Bacteroides and Dysgonomonas isolates could degrade starch, pectin, and/or cellulose and grow in the presence of these substrates as a single sugar source. Plant polysaccharides enrich P. americana diets, and many of these gut isolates are well equipped to exploit host dietary inputs and potentially contribute to gut community and host nutrient accessibility. IMPORTANCE Gut microbes are increasingly being recognized as critical contributors to nutrient accessibility in animals. The globally distributed omnivorous American cockroach ( Periplaneta americana ) harbors many bacterial phyla (e.g., Bacteroidetes ) that are abundant in vertebrates. P. americana thrives on a highly diverse plant-enriched diet, making this insect a rich potential source of uncharacterized polysaccharolytic bacteria. We have cultivated, completely sequenced, and functionally characterized several novel Bacteroidetes species that are endemic to the P. americana gut, and many of these isolates can degrade simple and complex polysaccharides. Cultivation and genomic characterization of these Bacteroidetes isolates further enable deeper insight into how these taxa participate in polysaccharide metabolism and, more broadly, how they affect animal health and development. 

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4. eCAMI: simultaneous classification and motif identification for enzyme annotation

   https://doi.org/10.1093/bioinformatics/btz908  

   Xu, Jing ; Zhang, Han ; Zheng, Jinfang ; Dovoedo, Philippe ; Yin, Yanbin ; Xu, ed., Jinbo ( December 2019 , Bioinformatics)

   Carbohydrate-active enzymes (CAZymes) are extremely important to bioenergy, human gut microbiome, and plant pathogen researches and industries. Here we developed a new amino acid k-mer-based CAZyme classification, motif identification and genome annotation tool using a bipartite network algorithm. Using this tool, we classified 390 CAZyme families into thousands of subfamilies each with distinguishing k-mer peptides. These k-mers represented the characteristic motifs (in the form of a collection of conserved short peptides) of each subfamily, and thus were further used to annotate new genomes for CAZymes. This idea was also generalized to extract characteristic k-mer peptides for all the Swiss-Prot enzymes classified by the EC (enzyme commission) numbers and applied to enzyme EC prediction.

   This new tool was implemented as a Python package named eCAMI. Benchmark analysis of eCAMI against the state-of-the-art tools on CAZyme and enzyme EC datasets found that: (i) eCAMI has the best performance in terms of accuracy and memory use for CAZyme and enzyme EC classification and annotation; (ii) the k-mer-based tools (including PPR-Hotpep, CUPP and eCAMI) perform better than homology-based tools and deep-learning tools in enzyme EC prediction. Lastly, we confirmed that the k-mer-based tools have the unique ability to identify the characteristic k-mer peptides in the predicted enzymes.

   https://github.com/yinlabniu/eCAMI and https://github.com/zhanglabNKU/eCAMI.

   Supplementary data are available at Bioinformatics online.

    

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5. Polyphenol Utilization Proteins in the Human Gut Microbiome

   https://doi.org/10.1128/AEM.01851-21  

   Zheng, Bo ; He, Yinchao ; Zhang, Pengxiang ; Huo, Yi-Xin ; Yin, Yanbin ( February 2022 , Applied and Environmental Microbiology)

   Ercolini, Danilo (Ed.)

   ABSTRACT Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (unified human gastrointestinal protein) databases. All PUP seeds and homologs were classified into protein classes, families, and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains, and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are consumed by the African population more commonly than by other populations, such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. IMPORTANCE Long-term consumption of polyphenol-rich foods has been shown to lower the risk of various human diseases, such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which contains various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations. 

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