Information on EC 2.3.1.86 - fatty-acyl-CoA synthase system

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FAS

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FAS1

fas2

fatty acid synthase

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fatty-acyl-CoA synthase

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yeast fatty acid synthase

acetyl-CoA + n malonyl-CoA + 2n NADPH + 4n H+ = long-chain-acyl-CoA + n CoA + n CO2 + 2n NADP+

6 entries

Acyl group transfer

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decarboxylation

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redox reaction

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KEGG

Fatty acid biosynthesis

MetaCyc

fatty acid biosynthesis initiation (type I), mycolate biosynthesis, palmitate biosynthesis I (type I fatty acid synthase), stearate biosynthesis III (fungi), superpathway of mycolate biosynthesis

acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing)

The enzyme from yeasts (Ascomycota and Basidiomycota) is a multi-functional protein complex composed of two subunits. One subunit catalyses the reactions EC 1.1.1.100, 3-oxoacyl-[acyl-carrier-protein] reductase and EC 2.3.1.41, beta-ketoacyl-[acyl-carrier-protein] synthase I, while the other subunit catalyses the reactions of EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase, EC 2.3.1.39, [acyl-carrier-protein] S-malonyltransferase, EC 4.2.1.59, 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 1.3.1.10, enoyl-[acyl-carrier-protein] reductase (NADPH, Si-specific) and EC 1.1.1.279, (R)-3-hydroxyacid-ester dehydrogenase. The enzyme system differs from the animal system (EC 2.3.1.85, fatty-acid synthase system) in that the enoyl reductase domain requires FMN as a cofactor, and the ultimate product is an acyl-CoA (usually palmitoyl-CoA) instead of a free fatty acid.

9045-77-6

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acetyl-CoA + 7 malonyl-CoA + 7 NADH + 7 NADPH + 14 H+

palmitoyl-CoA + 7 CoA + 7 CO2 + 7 NAD+ + 7 NADP+ + 7 H2O

13 entries

acetyl-CoA + malonyl-CoA + NADH + NADPH

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decanoyl-CoA + malonyl-CoA + NADPH + H+

?

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Substrates: -
Products: -

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lauroyl-CoA + malonyl-CoA + NADPH + H+

?

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Substrates: -
Products: -

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myristoyl-CoA + malonyl-CoA + NADPH + H+

?

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Substrates: -
Products: -

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octanoyl-CoA + malonyl-CoA + NADPH + H+

?

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Substrates: -
Products: -

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additional information

?

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acetyl-CoA + malonyl-CoA + NADH + NADPH

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4'-phosphopantetheine

FMN

NADH

NADPH

1,3-Dibromo-2-propanone

5,5'-dithio-bis(2-nitrobenzoic acid)

cerulenin

iodoacetamide

methylamine tungstad

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inactivation within 24 h

N-ethylmaleimide

p-chloromercuribenzoate

Euglena gracilis

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complete inhibition of type II fatty acid synthase at 1 mM

486871

thiolactomycin

Lathyrus oleraceus

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antibiotic and it's analogues, 50% inhibition of the overall activity at 0.17 mM, effect of antibiotic on compounds of the enzyme

487616

3-O-methylmannose

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0.1 mM, lowers Km 4fold, activation by relieving product inhibition by binding long-chain acyl-CoA

6-O-methylglucose

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0.1 mM, lowers Km 4fold, activation by relieving product inhibition by binding long-chain acyl-CoA

ATP

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stimulatory at suboptimal but not at saturating substrate concentrations

cysteine

glutathione

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activation

Triton X-100

additional information

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no activation by DTT

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0.09 - 0.8

acetyl-CoA

0.83

decanoyl-CoA

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0.05

lauroyl-CoA

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0.0096 - 0.04

malonyl-CoA

0.4

myristoyl-CoA

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0.067

NADPH

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0.33

octanoyl-CoA

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0.13

palmitoyl-CoA

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additional information

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0.062

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substrates: acetoacetyl-cysteamine, malonyl-CoA and NADPH

0.31

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FAS-A

487590

0.37

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FAS-B

487590

0.375

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0.53

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0.8 - 0.83

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malonyl-CoA

1.25 - 1.75

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substrate: C2-unit

1.5 - 2.5

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1.5 - 4

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1.6

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substrates: acetoacetyl-CoA, malonyl-CoA and NADPH H

2.5 - 3.5

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NADPH

3

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487603, 487608

additional information

6.5 - 7

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22

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beta-ketoacyl synthetase activity, assay at

25

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assay at

487603, 487608, 487609

37

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assay at

487604, 487605

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-

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487590, 487591, 757736

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-

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type II fatty acid synthase complex, expression in Sf9 cells

Karenia brevis Gerd Hansen

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Karenia brevis

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736682

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736682

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Komagataella pastoris

A0A1B2J6J3 i.e subunit alpha (FAS2), A0A1B2J839 i.e. subunit beta (FAS1)

779326

A0A1B2J6J3; A0A1B2J839

UniProt

Lachancea kluyveri

fatty acid synthase alpha-subunit

SwissProt

pea

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Mycolicibacterium smegmatis

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486863, 487611

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Photobacterium profundum SS9

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Photobacterium profundum

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487613

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487613

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Pseudomonas aeruginosa

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735449

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Saccharomyces cerevisiae ATCC 204508

12 entries

Saccharomyces cerevisiae BY4742

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748546

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Saccharomyces cerevisiae Fleishmann

wild type and protease-negative pep4-mutant

Saccharomyces cerevisiae X-2180-A

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-

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Spinacia oleracea

spinach

487617

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Thermomyces lanuginosus

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-

-

-

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Highest Expressing Human Cell Lines

Filter by:

Cell Line Links

Gene Links

malfunction

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construction of Fas2 disruptants influences virulence, unability to form normal biofilms

metabolism

physiological function

additional information

Komagataella phaffii GS115

P07149

glycolytic enzyme Tdh3p interacts with the FAS1 mRNA, and is necessary for the periodic abundance of Fas1 in the cell cycle

28 entries

Saccharomyces cerevisiae S288C

1390000

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sedimentation velocity data

180000

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alpha6,beta6, 6 * 185000 + 6 * 180000, SDS-PAGE

185000

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alpha6,beta6, 6 * 185000 + 6 * 180000, SDS-PAGE

203000

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alpha6,beta6, 6 * 213000 + 6 * 203000, Tris-glycine-SDS-PAGE

487574, 487603, 487607

213000

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alpha6,beta6, 6 * 213000 + 6 * 203000, Tris-glycine-SDS-PAGE

487574, 487603, 487607

2300000

2370000

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sedimentation equilibrium method

2400000

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sedimentation velocity

487574, 487603, 487607

324900

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calculated from nucleotide sequence

487591

43000

Homo sapiens

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x * 46000, SDS-PAGE, x * 43000, calculated

46000

Homo sapiens

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x * 46000, SDS-PAGE, x * 43000, calculated

additional information

11 entries

?

Homo sapiens

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x * 46000, SDS-PAGE, x * 43000, calculated

dodecamer

5 entries

hexamer

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homohexamer

487591

additional information

11 entries

phosphoprotein

P19097

residues S1440, S1640, and S1827 are phosphorylation sites, phosphomimetic mutations in these sites increase the biosynthesis of C18-containing lipids during fermentative growth

776958

cryo-EM structure, to 3.1 A resolution

Komagataella pastoris

A0A1B2J6J3; A0A1B2J839

779326

a gamma subunit of the 2.6 megadalton FAS16-FAS26 stabilizes a rotated FAS conformation and rearranges ACP domains from equatorial to axial positions. The gamma subunit spans the length of the FAS inner cavity, impeding reductase activities of FAS, regulating NADPH turnover by kinetic hysteresis at the ketoreductase, and suppressing off-pathway reactions at the enoylreductase. The gamma subunit delineates the functional compartment within FAS

P07149; P19097; Q12513

756369

crystal structure of yeast FAS reveals that this large, macromolecular assembly functions as a six-chambered reactor for fatty acid synthesis. Each of the six chambers functions independently and has in its chamber wall all of the catalytic units required for fatty acid priming, elongation, and termination, while one substrate-shuttling component, ACP, is located inside each chamber and functions like a swinging arm. Surprisingly, however, the step at which the reactor is activated must occur before the complete assembly of the particle since the PPT domain that attaches the pantetheine arm to ACP lies outside the assembly, inaccessible to ACP that lies inside. Remarkably, the architectural complexity of the FAS particle results in the simplicity of the reaction mechanisms for fatty acid synthesis

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685985

structure determined at 3.1 A resolution with its acyl carrier protein stalled at the active site of ketoacyl synthase. The structure shows the direct interaction of acyl carrier protein with one of the key catalytic centers in a multifunctional enzyme and suggest a model for substrate delivery that might apply to the other catalytic domains as well

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677130

structure of the Saccharomyces cerevisiae FAS determined at 3.1 A resolution with its acyl carrier protein stalled at the active site of ketoacyl synthase. The structure of the yeast FAS complex shows the direct interaction of acyl carrier protein with one of the key catalytic centers in a multifunctional enzyme and suggests a model for substrate delivery

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677130

5 A resolution

Thermomyces lanuginosus

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677122

crystal structure at 3.1 A resolution

Thermomyces lanuginosus

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677129

C1305A

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peripheral SH-group defective

I306A/G1250S

mutant displays best production of hexanoic acid, accounting for 90% of measured short-chain fatty acids, yield is 20 mg/l

I306A/G1250S/M1250W

mutant displays increased synthesis of short-chain fatty acids, yield is up to 66 mg/l

I306A/R1834K/F1279Y

mutant displays best production of octanoic acid, yield is 48 mg/l

I306A/R1834K/G1250S

mutant displays increased synthesis of short-chain fatty acids, yield is up to 118 mg/l

R1834K

S180G

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central SH-group defective

S5421Q

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malonyl/palmitoyl transferase defective

S819Q

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acyltransferase defective

T181G

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central SH-group defective

A45C

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about 5% reduction in overall enzyme activity

A45G

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about 15% reduction in overall enzyme activity

A45W

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about 10% reduction in overall enzyme activity

E41D

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about 10% reduction in overall enzyme activity

E41K

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no residual activity

V43I

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no reduction in overall enzyme activity

additional information

2-mercaptoethanol, inactivation during storage

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acylation of free protein amino groups leads to reversible dissociation into subunits

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low ionic strength leads to inactivation

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low ionic strength, 0.005 M, leads to dissociation into subunits, partially reactivated by increasing the ionic strength to 0.5 M

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PMSF ensures isolation of native enzyme

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under 100 atm nitrogen, at 4°C 1-20 h stable, 40% loss of activity after 40 h

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487604

under 100 atm oxygen, at 4°C 1-2 h stable, 48% and 90% loss of activity after 20 h and 40 h, respectively, DTT does not restore activity

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487604

-15°C, stable in 90% ammonium sulfate solution containing 0.1 M potassium phosphate, pH 6.5, and 1 mM DTT

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487602, 487605

-20°C, 1 month

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4°C, precipitate in 50% ammonium sulfate solution, several days

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-

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487601, 487605, 487609, 487618, 685985

900fold

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FAS-A and FAS-B

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487591

homogeneity

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isolation and sequencing of active-site peptides with transacylase activity

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487610

isolation of alpha- and beta-subunits

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487574, 487603

isolation of alpha- and beta-subunits by acylation

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isolation of alpha- and beta-subunits by citraconic and dimethylmaleic anhydride modification

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isolation of alpha- and beta-subunits by citraconic and dimethylmaleic anhydride modification or as 3,4,5,6-tetrahydrophthalate derivatives

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487603

isolation of peptides after proteolysis

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mutants

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partial purification of components

Euglena gracilis

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486871

purification of 2 structurally related but functionally differentiated fatty acid synthases: FAS-A and FAS-B, homogeneity

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487590

purification of acyl carrier protein

Escherichia coli

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486863

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5 entries

mutants

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transformation technique, plasmid YEpFAS2 transformed to and expressed in Escherichia coli maxi-cells

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absence of type I FASs that are unique from the polyketide synthases, while ketoacyl synthase domain proteins reside in the cytosol, raises the possibility that fatty acid synthesis may be carried out by protein complexes containing polyketide synthase-like ketoacyl synthase domains

hydrolysis under mild acidic condition leads to unmodified subunits, which can be reconstituted to form a complex displaying about 60% of the original activity

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low concentration of phosphate buffer causes dissociation into inactive species, reaggregation and reactivation can be partially achieved by dialysis against 0.5 M phosphate buffer

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analysis

Pseudomonas aeruginosa

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development of a high-throughput cellular bioluminescent reporter screen for inhibitors of the FASII pathway

735449

biofuel production

medicine

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potential treatment of infection of humans with Candida parapsilosis

synthesis