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DTSTAMP:20260411T190953
DTSTART:20180215T110000
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URL:https://murmitoyen.com/events/vanille/udem/detail/807822-genomic-enzymo
 logyr-strategy-for-the-discovery-of-novel-metabolic-pathways
LOCATION:Pavillon Roger-Gaudry \, 2900\, boul. Édouard-Montpetit\, Local M
 -415\, Montréal\, QC\, Canada
SUMMARY:Genomic Enzymology” Strategy for the Discovery of Novel Metabolic
  Pathways
DESCRIPTION:Cconférence prononcée par Xinshuai Zhang\, Ph.D. de l'Unive
 rsité d'Illinois.
\nRésumé : With the advances in genome sequencing tec
 hnologies\, we are now exposed to a large collection of protein sequences 
 that natural continues to evolve. The abundance of protein sequences repre
 sents an unprecedented opportunity for the biomedical and biotechnological
  societies. Such data can be exploited to provide targets for chemotherape
 utic agents\, and allow the advances in the fields of biocatalyst and biof
 uel. However\, achievement of this huge potential is confounded by the pro
 blem that reliable functions have only been assigned to a small and dimini
 shing fraction of protein sequences in the protein database. To address th
 is issue\, the Enzyme Function Initiative (EFI) which is a large-scale\, m
 ulti-institutional collaborative project was launched and the integrated 
 “genomic enzymology” strategy was established. Especially\, the “gen
 omic enzymology” web tools “Sequence Similarity Network (SSN) and “G
 enome Neighborhood Network (GNN)” were developed. SSNs are used to visua
 lize the sequence-function relationships in protein families and segregate
  the family into isofunctional clusters\; GNNs enable a user to retrieve\,
  display\, and interrogate the genome contexts of members of isofunctional
  SSN clusters so that the enzyme components of metabolic pathways can be i
 dentified. Experimentally determined ligand specificity of solute binding 
 protein (SBP) provides the first reactant in a metabolic pathway. In bacte
 rial\, the transporter genes are often co-located with genes encoding the 
 enzymes responsible for catabolism of the transported SBP ligand. Collecti
 vely\, ligand specificity of SBP\, synergetic analysis of SSNs and GNNs fa
 cilitates the large‑scale prediction of enzymatic activities and metabol
 ic pathways.
\nGuided by four TRAP SBPs that bind D/L-erythronate\, we ass
 igned novel ATP-dependent four-carbon acid sugar kinase functions to membe
 rs of the Domain of Unknown Function 1537 protein family (PF07005)\; we al
 so identified the related catabolic pathways to degrade D/L-threonate and 
 D-erythronate. In addition\, informed with the ligand specificities of thr
 ee ABC SBPs for D-apiose\, a ubiquitous branched-chain pentose in the rham
 nogalacturonan-II (RG-II) of plant cell walls\, four catabolic pathways in
 cluding one non-oxidative transketolase pathway and three oxidative pathwa
 ys for D-apiose/D-apionate were delineated. The non-oxidative transketolas
 e pathway can also be utilized by organisms from human gut microbiome. Sig
 nificantly\, the pathways involve several unusual enzymatic transformation
 s\, for example\, members of the functionally diverse RuBisCO superfamily 
 (PF00016) catalyze decarboxylation or transcarboxylation reactions. Member
 s of PGDH_C family (PF16896) catalyze the oxidative isomerization of D-api
 onate. The integrated “genomic enzymology” strategy\, as demonstrated 
 here\, is a powerful strategy for assigning enzymatic functions and elucid
 ating metabolic pathways.
\nAffiche de la conférence
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