1, StarOmics course,Lausanne, Monday November 19 th Training agenda Chemicals Reactions Enzymes...

1, StarOmics course,Lausanne, Monday November 19th

Training agenda

Outline

Part I:• Introduction• Data model

L-lysine biosynthesis• Pathway resources

UniPathway, KEGG, MetaCyc, Reactome, GO

Part II:• UniPathway tutorial

Gene Ontology: biological processhttp://amigo.geneontology.orgKEGGhttp://www.genome.jp/kegg/compound MetaCychttp://metacyc.org Reactomehttps://www.reactome.orgUniPathwayhttp://www.unipathway.org…

Metabolic pathway resources

– Dealing with the metabolic network as a whole is complex, and usage consists in decomposing the network into sub-parts, called metabolic pathways. Beside this pragmatic reason, another reason is that these pathways may be considered as elementary functional "modules" or building blocks. They can be combined, may have been conserved through evolution or may have evolved independently.

Metabolic pathways

– Dealing with the metabolic network as a whole is complex, and usage consists in decomposing the network into sub-parts, called metabolic pathways. Beside this pragmatic reason, another reason is that these pathways may be considered as elementary functional "modules" or building blocks. They can be combined, may have been conserved through evolution or may have evolved independently.

– A metabolic pathway can be common to several organisms, meaning that the same set of reactions and enzyme families occurs in these organisms.

However, some deviations (alternative reactions) can be observed for a specific organism (or a group of organisms), leading to the notion of "variants”.

Metabolic pathways

Variations in the biosynthesis of L-lysine

Yuchen Liu et al. J Bacteriol. 2010, 192:3304-3310.

DAP pathway

Torruella et al. J Mol. Evol. 2009, 69:240-248.

AAA pathway

7, StarOmics course,Lausanne, Monday November 19th 7

L-lysine biosynthesis via DAP pathway L-lysine biosynthesis via AAA pathway

L-alpha-aminoadipate from 2-oxoglutarate

LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate

(acetylase route)

LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate(aminotransferase route)

(succinylase route)

L-lysine from DL-2,6 diaminopimelate

(S)-tetrahydrodipicolinate fromL-aspartate

DL-2,6-diaminopimelate fromLL-2,6diaminopimelate

DL-2,6-diaminopimelate from(S)-tetrahydrodipicolinate

L-lysine from L-alpha-aminoadipate(fungal route)

L-lysine from L-alpha-aminoadipate

(Thermus route)

L-lysine biosynthesis

DAP pathway

AAA pathway

L-Lysine

variant I II III IV V VII 9 6 5 0 0 6II 10 5 0 0 6III 7 0 0 5IV 9 5 0V 10 0VI 7

Individual Amino Acids BiosynthesisLysine biosynthesis

• Lysine biosynthesis I• Lysine biosynthesis II • Lysine biosynthesis III • Lysine biosynthesis IV • Lysine biosynthesis V• Lysine biosynthesis VI

AAA pathway (2 variants)

DAP pathway (4 variants)

I II III

Gene Ontology: biological processhttp://amigo.geneontology.orgKEGGhttp://www.genome.jp/kegg/compound MetaCychttp://metacyc.org Reactomehttps://www.reactome.orgUniPathwayhttp://www.unipathway.org…

Metabolic pathway resources

L-lysine biosynthesis via DAP pathway L-lysine biosynthesis via AAA pathway

(acetylase route)

LL-2,6 diaminopimelate from(S)-tetrahydrodipicolinate(aminotransferase route)

(succinylase route)

L-lysine from DL-2,6 diaminopimelate

(S)-tetrahydrodipicolinate fromL-aspartate

DL-2,6-diaminopimelate fromLL-2,6diaminopimelate

DL-2,6-diaminopimelate from(S)-tetrahydrodipicolinate

L-lysine from L-alpha-aminoadipate(fungal route)

(Thermus route)

L-lysine biosynthesis

UniPathway concepts

UCR03444: Left-to-Right direction is used in UER00029

UCR04371: Right-to-Left direction is used in UER00029

UER00028 (EC 2.3.3.14)= UCR00271 [LR]

UER00029 (EC 4.2.1.36)= UCR03444 [LR] + UCR04371 [RL]

ULS00012L-a-aminoadipate from 2-oxoglutarate

UCR00271: Left-to-Right direction is used in UER00028

Protein-Reaction curation is performed in UniProt

UniPathway provides a structured controlled vocabulary for the annotation of pathway information within UniProtKB protein records.

L-lysine biosynthesis via AAA pathway

UniPathway : label construction

An enzymatic reaction is labelled by its relative position in the sub-pathway : step n/m

step 1/4

step 2/4

step 3/4

step 4/4

L-alpha aminoadipate from 2-oxoglutarate

A sub-pathway is labelled by its terminal compounds :

product from substrate

A pathway is labelled by its terminal compound(s)“product biosynthesis” | “substrate degradation” [via xxx pathway]

CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via AAACC pathway; L-lysine from L-alpha-aminoadipate (Thermus route): stepCC 5/5.

Acetyl-lysine deacetylase (T.thermophilus) (LYSK_THET2; Q8VUS5)

UniProt Headlineshttp://www.uniprot.org/news/2009/01/20/release

UPA00033 L-lysine via AAA pathway

UPA00402 Amino-acid biosynthesis

ULS00014 L-lysine from L-alpha-aminoadipate (Thermus route)

UER00039 step 5/5

CC-!-PATHWAY: super-pathway; pathway; sub-pathway: enzymatic-reaction.

UniPathway : label construction

General annotation : Pathway link to UniPathway web site

Pathway explorationhttp://www.unipathway.org

Chemical view

Taxonomy view

Protein view

glutamine glutamate+

pyruvateO O

anthranilatechorismate

Molecular enzyme :TrpEDEnzyme classification : EC 4.1.3.27

Anthranilate synthase

How a given pathway is distributed into kingdoms, species,…?

Genomic view

genea geneb

How genes coding for the enzymes of a metabolic pathway are distributed into the genome?

OBIWarehouse

TrEMBL reference proteomes

Swiss-Prot

UniPathway

Calculation

NCBI. RefSeq genomes

GeneOntology

Enzyme /IntEnz

Taxonomy. NCBI

Data update:sync. with UniProt releases

UniProtKB (part.)

BioCyc Eco/MetaCyc

KEGG LIGAND

UniProt complete proteomes

Protein view

Chemical view

Ontology view

PathwaySub-pathwayEnz-reaction

Genomic viewTaxonomy view

UniPathway tutorial

UniPathway short tour http://www.unipathway.org

The home page is organized in 8 sections accessible through tabs

List of pathways for a given species

List of compounds used in UniPathway

List of pathways in UniPathway

Search UniPathway

Quick search: lysine

Linear Sub-pathway: ULS

Pathway: UPA

Enzymatic-Reaction: UER

Action: Click on Quick search tabthen enter lysine in the UniPathway text field then click on Go button

Browse pathway – compound - organism

Table widget: known bug

if you encounter this error message just reload the web page

Browse organism

Action: Enter ECOL then select ECOLI then click on Go button

Browse organism provides the list of metabolic pathways for a selected organism

oscode=ECOLI

UniProtKB/Swiss-Prot annotation(reviewed)

Action: Click again on Quick searchthen click on UPA00034 (L-lysine biosynthesis via DAP pathway)

Browse one pathway

UniPathway: Pathway: Overview

tabs sections

Action: Click on map00300 to open the KEGG map with highlighted reactions

upid=UPA00034

Lysine biosynthesis via DAP pathway in Acinetobacter

Click on ACIAD (Acinetobacter) – the scientific name is given in the tooltip

UniPathway:Pathway: Genome view

Thank you for your attention!

1, StarOmics course,Lausanne, Monday November 19 th Training agenda Chemicals Reactions Enzymes...

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