Table 1 Table of DEPs in T. bilis MMM721 DEPs in BHIGL + Bile, BHIGL + TCDCA, and BHIGL + TCA compared to BHIGL only control. Bolded values were DEPs in BHIGL + Bile, BHIGL + TCDCA, or BHIGL + TCA. The COG category assignments and protein descriptions were provided by EggNOG-mapper

C: Energy production and conversion

ONGNNMAF_01437

F(1)F(0) ATP synthase produces ATP from ADP in the presence of a proton or sodium gradient. F-type ATPases consist of two structural domains, F[1] containing the extramembraneous catalytic core and F(0) containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F is coupled via a rotary mechanism of the central stalk subunits to proton translocation

ONGNNMAF_01709

Activation of pyruvate formate-lyase under anaerobic conditions by generation of an organic free radical, using S- adenosylmethionine and reduced flavodoxin as cosubstrates to produce 5'-deoxy-adenosine

ONGNNMAF_01722

Nitroreductase family

ONGNNMAF_01745

Dehydrogenase

ONGNNMAF_01769

Belongs to the nitrite and sulfite reductase 4Fe-4S domain family

ONGNNMAF_02115

Belongs to the class-II pyridine nucleotide-disulfide oxidoreductase family

ONGNNMAF_02459

SUF system FeS assembly protein, NifU family

ONGNNMAF_02607

belongs to the iron- containing alcohol dehydrogenase family

D: Cell cycle control, cell division, chromosome partitioning

ONGNNMAF_00642

Involved in protein export. Acts as a chaperone by maintaining the newly synthesized protein in an open conformation. Functions as a peptidyl-prolyl cis–trans isomerase

ONGNNMAF_01411

Peptidase family M23

E: Amino acid transport and metabolism

ONGNNMAF_00140

Cleaves the N-terminal amino acid of tripeptides

ONGNNMAF_02259

Peptidase dimerisation domain

ONGNNMAF_02452

Aminopeptidase P, N-terminal domain

F: Nucleotide transport and metabolism

ONGNNMAF_00874

Belongs to the cytidylate kinase family. Type 1 subfamily

ONGNNMAF_01593

Catalyzes the synthesis of GMP from XMP

ONGNNMAF_01630

Belongs to the purine pyrimidine phosphoribosyltransferase family

ONGNNMAF_01948

Belongs to the d-alanine–d-alanine ligase family

G: Carbohydrate transport and metabolism

ONGNNMAF_00074

Psort location Cytoplasmic, score 9.98

ONGNNMAF_00350

Psort location Cytoplasmic, score

ONGNNMAF_00457

M42 glutamyl aminopeptidase

ONGNNMAF_00502

Belongs to the glycosyl hydrolase 13 family

ONGNNMAF_01096

PTS system, glucose subfamily, IIA

ONGNNMAF_01444

Psort location Cytoplasmic, score 8.87

ONGNNMAF_01872

Fructose-1,6-bisphosphatase

ONGNNMAF_01935

Catalyzes the conversion of glucosamine-6-phosphate to glucosamine-1-phosphate

ONGNNMAF_02092

Psort location Cytoplasmic, score

ONGNNMAF_02192

Domain of unknown function (DUF5110)

ONGNNMAF_02194

Melibiase

ONGNNMAF_02435

Bacterial extracellular solute-binding protein

ONGNNMAF_02481

Bacterial extracellular solute-binding protein

H: Coenzyme transport and metabolism

ONGNNMAF_00285

6-pyruvoyl tetrahydropterin synthase

ONGNNMAF_02112

Catalyzes the ATP- as well as the pyrophosphate- dependent phosphorylation of a specific serine residue in HPr, a phosphocarrier protein of the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS). HprK P also catalyzes the pyrophosphate-producing, inorganic phosphate-dependent dephosphorylation (phosphorolysis) of seryl-phosphorylated HPr (P- Ser-HPr). The two antagonistic activities of HprK P are regulated by several intracellular metabolites, which change their concentration in response to the absence or presence of rapidly metabolisable carbon sources (glucose, fructose, etc.) in the growth medium. Therefore, by controlling the phosphorylation state of HPr, HPrK P is a sensor enzyme that plays a major role in the regulation of carbon metabolism and sugar transport it mediates carbon catabolite repression (CCR), and regulates PTS-catalyzed carbohydrate uptake and inducer exclusion

ONGNNMAF_02537

Catalyzes the synthesis of ADP-glucose, a sugar donor used in elongation reactions on alpha-glucans

I: Lipid transport and metabolism

ONGNNMAF_00468

Dehydrogenase

J: Translation, ribosomal structure and biogenesis

ONGNNMAF_00551

Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction alanine is first activated by ATP to form Ala- AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) via its editing domain

ONGNNMAF_00686

Belongs to the universal ribosomal protein uS2 family

ONGNNMAF_00699

This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site

ONGNNMAF_00877

Belongs to the pseudouridine synthase RsuA family

ONGNNMAF_01070

amino acids such as threonine, to avoid such errors, it has a posttransfer editing activity that hydrolyzes mischarged Thr-tRNA(Val) in a tRNA-dependent manner

ONGNNMAF_01175

Belongs to the class-I aminoacyl-tRNA synthetase family

ONGNNMAF_01458

ATPase that binds to both the 70S ribosome and the 50S ribosomal subunit in a nucleotide-independent manner

ONGNNMAF_01634

RNA binding protein, contains ribosomal protein S1 domain

ONGNNMAF_01830

Arginyl-tRNA synthetase

ONGNNMAF_01892

Forms part of the ribosomal stalk which helps the ribosome interact with GTP-bound translation factors

ONGNNMAF_01894

Forms part of the ribosomal stalk, playing a central role in the interaction of the ribosome with GTP-bound translation factors

ONGNNMAF_01901

Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post- translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome

ONGNNMAF_01904

One of the primary rRNA binding proteins, it binds directly near the 3’-end of the 23S rRNA, where it nucleates assembly of the 50S subunit

ONGNNMAF_01909

The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome

ONGNNMAF_01910

Binds the lower part of the 30S subunit head. Binds mRNA in the 70S ribosome, positioning it for translation

ONGNNMAF_01911

Binds 23S rRNA and is also seen to make contacts with the A and possibly P site tRNAs

ONGNNMAF_01913

One of the primary rRNA binding proteins, it binds specifically to the 5’-end of 16S ribosomal RNA

ONGNNMAF_01914

Binds to 23S rRNA. Forms part of two intersubunit bridges in the 70S ribosome

ONGNNMAF_01915

One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit

ONGNNMAF_01920

This is one of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance

ONGNNMAF_01923

binds to the 23S rRNA

ONGNNMAF_02102

tRNA synthetases class I (E and Q), anti-codon binding domain

ONGNNMAF_02594

Psort location Cytoplasmic, score

ONGNNMAF_02602

One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit

ONGNNMAF_02642

Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions

K: Transcription

ONGNNMAF_00074

Psort location Cytoplasmic, score 9.98

ONGNNMAF_00373

Cold-shock DNA-binding domain protein

ONGNNMAF_00603

Negative regulator of class I heat shock genes (grpE- dnaK-dnaJ and groELS operons). Prevents heat-shock induction of these operons

ONGNNMAF_01042

Cold-shock DNA-binding domain protein

ONGNNMAF_02616

Psort location Cytoplasmic, score

L: Replication, recombination and repair

ONGNNMAF_01805

A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner

M: Cell wall/membrane/

envelope biogenesis

ONGNNMAF_00060

Choline/ethanolamine kinase

ONGNNMAF_00349

FMN-binding domain protein

ONGNNMAF_01300

Catalyzes the reduction of dTDP-6-deoxy-L-lyxo-4- hexulose to yield dTDP-L-rhamnose

O: Post-translational modification, protein turnover, and chaperones

ONGNNMAF_00204

Molecular chaperone. Has ATPase activity

ONGNNMAF_00641

ATP-dependent Clp protease ATP-binding subunit ClpX

ONGNNMAF_00848

PPIases accelerate the folding of proteins. It catalyzes the cis–trans isomerization of proline imidic peptide bonds in oligopeptides

ONGNNMAF_01227

Peroxiredoxin

ONGNNMAF_01975

peptidylprolyl isomerase

ONGNNMAF_02078

Prevents misfolding and promotes the refolding and proper assembly of unfolded polypeptides generated under stress conditions

ONGNNMAF_02457

SufB sufD domain protein

P: Inorganic ion transport and metabolism

ONGNNMAF_01712

Part of the ABC transporter complex MetNIQ involved in methionine import. Responsible for energy coupling to the transport system

ONGNNMAF_02637

TrkA N-terminal domain protein

Q: Secondary metabolites biosynthesis, transport, and catabolism

ONGNNMAF_00468

Dehydrogenase

S: Function unknown

ONGNNMAF_00252

Hypothetical protein

ONGNNMAF_00275

Hypothetical protein

ONGNNMAF_00984

Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

ONGNNMAF_01156

CYTH

ONGNNMAF_01493

Hypothetical protein

ONGNNMAF_01796

Psort location Cytoplasmic, score

ONGNNMAF_01808

S4 domain protein YaaA

ONGNNMAF_01956

An RNase that has 5'-3' exonuclease and possibly endonuclease activity. Involved in maturation of rRNA and in some organisms also mRNA maturation and or decay

ONGNNMAF_02132

Domain of unknown function (DUF4358)

ONGNNMAF_02639

An RNase that has 5'-3' exonuclease and possibly endonuclease activity. Involved in maturation of rRNA and in some organisms also mRNA maturation and or decay

T: Signal transduction mechanisms

ONGNNMAF_02581

Psort location Cytoplasmic, score

U: Intracellular trafficking, secretion, and vesicular transport

V: Defense mechanisms