[0001] The present invention relates to a production process by enzymatic catalysis mercaptans, especially méthylnnercaptan, from disulfides, especially dimethyl disulfide, and with hydrogen.

[0002] The mercaptans are very useful in many areas, such as flavorings, odorants for gas, chain transfer agents in polymerization, raw materials for the pharmaceutical and cosmetics industry for the synthesis of antioxidants , extreme pressure additives or antiwear for lubrication. These examples are in no way limiting the uses of mercaptans known today and that can be prepared using the method of the invention.

[0003] In particular, the first mercaptan, methyl mercaptan (CH 3 SH), is of great industrial interest, in particular as a raw material of methionine synthesis, essential amino widely used in animal feed acid. Methyl mercaptan is a raw material widely used for the synthesis of many other molecules.

[0004] The mercaptans may be synthesized by many methods such as alcohols sulfhydratation, catalytic or photochemical addition of hydrogen sulfide to unsaturated organic compounds, substitution with hydrogen sulfide halides, epoxides or organic carbonates, and the like.

[0005] In particular, the methyl mercaptan is commonly produced in large tonnage industrial scale from methanol and hydrogen sulphide according to reaction (1):

CH3OH + the H 2 S → CH3SH + the H 2 o (1)

[0006] These processes have the disadvantages of requiring methanol (CH3OH), to synthesize hydrogen sulfide (H2S, from hydrogen and sulfur, for example, hence the need to synthesize also hydrogen) and lead to by-products type dimethyl ether (CH3OCH3), dimethyl sulphide (CH3SCH3) and products of crackings and water, which implies numerous steps for the purification of methyl mercaptan.

[0007] For the description of processes based on these reactions as examples in patent applications such as WO2013092129, WO20081 18925, WO2007028708, WO2006015668, WO2004096760.

[0008] It may be economically interesting (to prevent methanol synthesis) will produce methyl mercaptan from carbon monoxide, hydrogen and hydrogen sulfide according to the synthesis scheme (2) below:

CO + 2 H2 + H2S→ CH3SH + H2O (2)

[0009] However, these methods have the disadvantages of requiring synthesis gas (CO / H 2) and thus to conduct a steam reforming a hydrocarbon source, having the right proportions of CO and H2 therefore can adjust the CO / h 2 ratio with the actual reaction of the "water gas" (CO + H2O → CO2 + H2), and synthesize h S.

[0010] These processes also generally lead to high levels of CO2 as a by-product, as well as methane, dimethyl sulfide and water. We find descriptions of these processes for example in patent applications such as US2010286448, US2010094059, US2008293974, US2007213564.

[0011] Still other methods have been described and combine different reactions such as:

• CS2 Training and h S from methane and sulfur (3):

CH4 + 4 S→ CS2 + 2 H2S (3)

• Hydrogenation of CS2 (4):

[0012] It is also possible to use the excess S h of the reactions (3) and (4) in the reactions with methanol (reaction 1) or of the synthesis gas (reaction 2) to give methyl mercaptan again.

[0013] These processes obviously combine the disadvantages described for reactions (1) and (2) with the added difficulty of having excess hydrogen to effect the reaction (4). We find descriptions of these processes in patent applications US201 1,015,443 or more specifically on the reaction (4) in the application WO2010046607.

[0014] The application provides a WO200196290 methyl mercaptan synthesis process directly from methane and h S with coproduction

hydrogen. This direct reaction between methane and h S is performed using a pulsed plasma with corona discharge. This application describes no synthesis example, it may seem hard to imagine an industrial synthesis process of methyl mercaptan large scale with this technology. Moreover this method requires the synthesis of S h if it is not available.

[0015] The EP0649837 patent application proposes in turn a methyl mercaptan synthesis process by catalytic hydrogenolysis, with transition metal sulfides, the dimethyl disulfide with hydrogen. This method, although effective, requires relatively high temperatures of the order of 200 ° C to obtain industrially interesting productivities.

[0016] The skilled person also knows that it is possible to prepare methyl mercaptan by acidification of an aqueous solution of sodium methyl mercaptide (ChbSNa). This method has the major drawback of generating large amounts of salts such as sodium chloride or sodium sulphate, depending on whether hydrochloric acid is used or sulfuric acid. The aqueous salt solutions are often very difficult to treat and traces of malodorous products remaining are that this method is hardly feasible industrially.

[0017] The processes of synthesis of higher methyl mercaptan to also have many disadvantages. Thus the substitution of alcohols with hydrogen sulfide often requires temperatures and high pressures, and results in unwanted olefins such byproducts, ethers and sulphides.

[0018] The catalytic or photochemical addition of hydrogen sulfide to unsaturated compounds is usually done under slightly milder conditions than previously but also leads to many by-products formed by isomerization of the feedstock by adding non- or regioselective double addition which gives sulphides. Finally, the substitution of halogenated led to processes that generate a lot of waste and saline discharges hardly compatible with industrial processes.

[0019] The present invention aims to provide a novel preparation method of mercaptans, especially methyl mercaptan, which does not have the disadvantages described in the known processes of the prior art and previously detailed.

[0020] More particularly, the present invention has as its first object the process for the preparation of a mercaptan of the formula R-SH, comprising at least the steps of: a) preparing a mixture comprising:

1) a disulphide of formula RSS-R ',

2) a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

3) a catalytic amount of an enzyme catalyzing the reduction of the disulfide bond created between two equivalents of said amino acid carrying a thiol group or thiol group of said peptide,

4) a catalytic amount of an enzyme catalyzing the reduction of

hydrogen,

5) a catalytic amount of a cofactor common to both enzymes

catalyzes the reduction and dehydrogenation

b) adding hydrogen,

c) carrying out the enzymatic reaction,

d) recovering the mercaptan of the formula R-SH and the mercaptan of the formula R'-SH, e) separation and possible purification of the mercaptan of the formula R-SH and / or mercaptan of the formula R'-SH.

[0021] The enzyme catalyzes the reduction of hydrogen can be of any type known to the art and for example the enzyme dehydrogenase hydrogen.

[0022] In general, the enzyme catalyzing the reduction of the disulfide bridge formed between two equivalents of said amino acid carrying a thiol group or thiol group of said peptide is a reductase enzyme. The term "reductase" is used in the following description for the explanation of the present invention.

[0023] Of the common cofactors for enzymes catalyzing both reduction and dehydrogenation (reductase and dehydrogenase) include as non-limiting examples cofactors flavin, nicotine and cofactors. We prefer to use the cofactor nicotinic especially the nicotinamide adenine dinucleotide (NAD), or better yet the nicotinamide adenine dinucleotide phosphate (NADPH). Cofactors listed above are advantageously used in their reduced forms (e.g., NADPH, H +) and / or their oxidized forms (for example NADP +), that is to say, they may be added in these reduced forms and / or oxidized in the reaction medium.

[0024] In one embodiment of the invention, the amino acid carrying a thiol group and / or peptide bearing a thiol group may be in the form of disulfide said amino acid and / or said peptide respectively (e.g. glutathione as glutathione disulfide).

[0025] The organization and order of additions of the various components of steps a) and b) of the preceding defined above can be achieved in different ways. In all cases, the enzymatic reaction of step c) is initiated by addition of one of the catalytic system components: an enzyme, or one of the compounds added in stoichiometric quantity (disulfide or hydrogen) is one of the compounds added in catalytic amount (amino acid carrying a thiol group or thiol group to the peptide or disulfide corresponding to said molecules or even cofactor).

[0026] Even more particularly, the present invention has as an object the method of preparing a mercaptan of the formula R-SH, comprising at least the steps of: a ') preparing a mixture comprising:

• a disulfide of formula feed-R '

• a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

• a catalytic amount of reductase enzyme corresponding to said amino acid carrying a thiol group or thiol group in said peptide,

• a catalytic amount of NADPH

b ') adding hydrogen with a catalytic amount of enzyme dehydrogenase hydrogen,

c ') carrying out the enzymatic reaction,

d ') recovering the mercaptan of the formula R-SH and the mercaptan of the formula R'-SH, e') separation and possible purification of the mercaptan of the formula R-SH and the mercaptan of the formula R'-SH.

[0027] In the context of the present invention, any disulfide having the general formula RSSR 'can be engaged in the mercaptan manufacturing process. In the general formula HR-R ', R and R', identical or different, represent independently of one another, a hydrocarbon, straight-chain, branched or cyclic, having from 1 to 20 carbon atoms, said chain being saturated or may carry one or more unsaturations in the form of double bed (s) or triple (s) link (s). R and R 'may also form, together with the sulfur atoms carrying them a cyclic molecule having from 4 to 22 atoms, preferably from 5 to 10 atoms.

[0028] In a preferred aspect, the radicals R and R ', identical or different, are selected independently of one another, from alkyl, cycloalkyl, aryl, alkylaryl, arylalkyl containing from 1 to 20 carbon atoms, preferably from 1 to 12 carbon atoms preferably from 1 to 6 carbon atoms, linear or branched, saturated or unsaturated, and optionally functionalized with one or more functions chosen, without limitation and by way of example among the function alcohol, aldehyde, ketone, acid, amide, nitrile, ester or surrogate functions of sulfur, phosphorus, silicon or halogen.

[0029] The disulfide of the formula RSSR 'is likely to be reduced according to the method of the invention, mercaptan of the formula R-SH and mercaptan of the formula R'-SH. When R is different from R ', is called asymmetric disulfide, and when R and R' are the same, it is called symmetrical disulfide. In the case of symmetrical disulfides RSSR, the method of the invention leads to a mercaptan of the formula R-SH. According to a particularly preferred embodiment of the invention is implemented dimethyl disulfide (DMDS) to produce methyl mercaptan CH 3 SH.

[0030] In the case of unsymmetrical disulfide RSS-R ', the process of the invention leads to a mixture of the formulas of mercaptans R-SH and R'-SH which can be either used as such or subjected to one or more well known separation operations to those skilled in the art, for example distillation.

[0031] It is also possible to implement the process of the invention mixtures of one or more disulfides, symmetrical and / or asymmetrical. Possible disulfide mixtures can understand the DSO ( "disulfide Oils" in English), said DSO thus finding a potential valuation quite interesting.

[0032] According to the method of the invention, the mercaptan products are generally recovered in the form of a solid, a liquid and / or gas.

[0033] The production method according to the invention is based on the enzymatic reduction of the disulfides, especially dimethyl disulfide, with hydrogen, according to the reaction illustrated with dimethyl disulfide to methyl leading:

CH3SSCH3 + the H 2 2 CH The 3 sh

[0034] It has now been discovered that this reaction is readily catalyzed by the enzyme system implementing a thiol group to amino acid or a thiol group in the peptide, e.g., glutathione, as a complex (amino acid or peptide) / corresponding reductase enzyme, regenerated with hydrogen, as described in Figure 1 herein.

[0035] Thus according to the Figure 1 illustration, the peptide (example shown the "glutathione") reduces the disulfide ( "DMDS" shown) mercaptan ( "methyl" shown) by transforming into disulfide-bonded peptide ( " glutathione disulfide "shown). The reductase enzyme ( "glutathione reductase" shown, EC 1 .8.1 .7 or EC 1 .6.4.2) regenerates the peptide (glutathione) and the same enzyme is regenerated by a redox enzyme complex known to those skilled the art, such as NADPH / NADP + complex (nicotine adenine dinucleotide phosphate (reduced form and oxidized form)). In its turn NADP + to NADPH is regenerated by means of the enzyme "Hydrogen dehydrogenase" (EC 1 .5 .12.1) with hydrogen. The proton released by the hydrogen s'" After reaction with NADPH and function mercaptide formed becomes a mercaptan function.

[0036] In other words, the peptide ( "glutathione" shown) reduces the disulfide ( "DMDS" shown) mercaptan ( "methyl" shown) by transforming into disulfide-bonded peptide ( "glutathione disulfide" shown) . The enzyme catalyzing the reduction ( "glutathione reductase" shown with the examples of enzyme classification number EC 1 .8.1 .7 or EC 1 .6.4.2) regenerates the peptide ( "GSH") while oxidizing the cofactor ( " NADPH, H + "shown). The oxidized form ( "NADP +" shown) is then reduced using an oxidation-reduction enzyme complex, called "recycle", well known to those skilled in the art and comprising the dehydrogenase enzyme involved ( "dehydrogenase hydrogen "shown with the example of enzyme classification number EC 1 .1 .1 .47) and hydrogen. The proton released by the hydrogen accumulates because it reacts directly on the function mercaptide formed during the reaction catalyzed by the reductase enzyme used.

[0037] According to one embodiment particularly adapted, the system glutathione / glutathione disulfide associated with the glutathione reductase enzyme of the present invention allows to reduce the DMDS methyl mercaptan.

[0038] Glutathione is a tripeptide widely used in biology. This species in reduced form (GSH) and oxidized (glutathione disulfide) forms an important redox couple in the cells. So glutathione is vital to remove heavy metals organizations. For example, the application WO05107723 describes a formulation in which glutathione is used to form a chelate preparation, patent US4657856 teaches that glutathione also used to destroy peroxides such ΙΉ2Ο2 H2O via glutathione peroxidase. Finally glutathione also reduces disulfide bonds in proteins (Rona Chandrawati, "Triggered Cargo Release Encapsulated by Enzymatic Catalysis in Capsosomes" Nano Lett (1 201), Vol. 1 1, 4958-4963).

[0039] According to the method of the invention, a catalytic amount of amino acid carrying a thiol group or thiol group to peptide, is implemented for the production of mercaptans from disulfides.

[0040] Among the amino acids thiol group of carriers used in the process of the present invention include, by way of non-limiting examples the cysteine ​​and homocysteine. The redox enzyme systems used to regenerate the catalytic cycle in the same way, these cases are in the system cysteine ​​/ cystine reductase EC 1 .8.1 .6, homocysteine ​​and / homocysteine ​​reductase.

[0041] Among the thiol group of bearing peptides used in the process of the present invention include, by way of non-limiting examples glutathione and thioredoxin. Glutathione system / glutathione reductase, described above, can thus be replaced by the thioredoxin system (CAS no. 52500-60-4) / thioredoxin reductase (EC 1 .8.1 .9 or EC 1 .6.4.5).

[0042] The glutathione and glutathione system / glutathione reductase are especially preferred for the present invention, due to the ease of supply and the costs thereof.

[0043] In the method according to the invention, hydrogen can be added to the reaction medium by any means known to those skilled in the art, for example by bubbling in the reaction medium which is preferably an aqueous-organic reaction medium. The hydrogen pressure in the reactor corresponds to the pressure of the reaction medium itself, which is defined below.

[0044] The enzyme used is hydrogen dehydrogenase enzyme, also well known to those skilled in the art.

[0045] In the method according to the invention only the disulfide (s) and hydrogen are used in stoichiometric amount, all other components (amino acid or peptide cofactor (e.g., NADPH) and the 2 enzymes) are used in catalytic amount.

[0046] The benefits of the process of the invention are numerous. These benefits include the ability to work in aqueous or aqueous solution under very mild conditions of temperature and pressure and pH conditions close to neutrality. All these conditions are typical of a biocatalytic process called "green" or "sustainable."

[0047] Another advantage when the process uses dimethyl disulfide is as methyl product, which is in the gaseous state under the reaction conditions, leaves the reaction medium as and when it is formed, possibly accompanied hydrogen that has not reacted. Methyl mercaptan can be used directly in the reactor outlet in a downstream application if unreacted hydrogen does not interfere therein. If the skilled person will easily separate hydrogen unconverted methyl mercaptan. It can also be easily liquefied cryogenic example if you want to isolate.

[0048] Dimethyl disulphide (DMDS) can be produced on a different site from methyl mercaptan and an oxidant such as oxygen, sulfur or oxygenated water for example, or from dimethyl sulfate and sodium disulfide. DMDS can also come from a source of "Disulfide Oils" (OSR), as indicated above, then purified, for example by reactive distillation, as described in WO2014033399 request. Note that the DSO can also be used as such, without the need for purification between the disulfide component. One then obtains a mixture of mercaptans by applying the method of the invention.

[0049] When DMDS is used as the disulfide, the method according to the invention may then be considered as a method for preventing the transport of methyl mercaptan from its production site by industrial existing channels, to its site of use if they are different. In fact, methyl mercaptan is a gas at room temperature, highly toxic and smelly which greatly complicates its transportation already highly regulated unlike DMDS. The process described in the present invention may therefore be used to produce methyl mercaptan directly on the use of the latter site.

[0050] The DMDS being consumed in the reaction and exiting the methyl mercaptan from the reaction medium as and when it is formed, without hydrogen, or with hydrogen unconverted, no product accumulates in the reaction medium, in assuming a continuous hydrogen supply and DMDS. It is not necessary to recycle the catalyst system, in terms of products entering and leaving the reactor.

[0051] In the case of other disulfide, based on the dot formed mercaptan boiling and its solubility in the reaction medium, the mercaptan may optionally decanted the reaction medium to be easily separated by well known techniques of art. Otherwise it may be isolated from the reaction medium, also by any means known in the art.

[0052] In general, the reaction temperature is within a range from 10 ° C to 50 ° C, preferably between 15 ° C and 45 ° C, more preferably between 20 ° C and 40 ° C.

[0053] The pH of the reaction may be between 6 and 8.5, preferably between 7.0 and 8.0. The pH of the reaction medium may be adjusted using a buffer. So Most preferably, one will choose the pH of a medium buffered to a value between 7.5 and 8.0.

[0054] The pressure used for the reaction can range from a reduced pressure relative to the atmospheric pressure to several bars (several hundred kPa), depending on the reagents used and the equipment used. Preferably, a pressure from atmospheric pressure will be used at 20 bar (2 MPa) and more preferably it will work under a pressure ranging from atmospheric pressure to 3 bars (300 kPa).

[0055] The method of the invention can be carried out batchwise or continuously in a reactor made of glass or metal depending on the operating conditions and reagents used. Preferably we choose a semi-continuous process in which hydrogen is added as and when it is consumed in the reaction.

[0056] The molar ratio hydrogen / disulfide is ideal stoichiometry (molar ratio = 1) but may range from 0.01 to 100 if the skilled person can find an interest, such as continuous addition of hydrogen, while the disulfide is introduced from the beginning into the reactor. Preferably this molar ratio is chosen between 1 and 20 globally on the entire reaction.

[0057] The hydrogen that is not converted may be recycled to the reactor outlet to the reactor inlet, up to total exhaustion. One can also consider a loop with hydrogen and (s) mercaptan (s) formed (s), until hydrogen has completely converted (s) disulfide (s). As a result, the end of the reaction when all of dimethyl disulfide is converted, exit gases contain almost exclusively methyl.

[0058] The elements present in a catalytic amount in the mixture prepared in step a) above (amino acid carrying a thiol group or thiol group to peptide, reductase enzyme, cofactor (e.g., NADPH)) are readily available commercially or can be prepared by techniques well known in the art. These different elements may be in solid or liquid form and may most preferably be dissolved in water to be used in the method of the invention. The enzymes used can also be grafted on a support (if the supported enzymes).

[0059] The aqueous solution of enzyme complex comprising the amino acid or peptide can also be reconstituted by methods known to those skilled in the art, for example by permeabilization of cells which contain these elements. This aqueous solution having a composition given in Example 1 the following may be used in weight contents of between 0.01% and 20% based on the total weight of the reaction medium. Preferably we use a content of between 0.5% and 10%.

[0060] According to another aspect, the present invention relates to the use of an aqueous solution of enzyme complex comprising an amino acid carrying a thiol group as defined above or a peptide bearing a thiol function such as defined above, for the synthesis of a mercaptan from a disulfide.

[0061] The mixture can be used for step a) of the process described above and comprising:

1) a disulphide of formula RSS-R ',

2) a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

3) a catalytic amount of an enzyme catalyzing the reduction of the bridge

disulfide created between two equivalents of said amino acid carrying a

thiol group or thiol group of said peptide,

4) optionally a catalytic amount of an enzyme catalyzing the reduction of the hydrogen,

5) a catalytic amount of a cofactor common to both enzymes catalyzing the reduction and dehydrogenation,

6) and optionally hydrogen,

where R and R 'are as defined above,

is new and as such is part of the present invention.

[0062] In one embodiment of the invention, the amino acid carrying a thiol group and / or peptide bearing a thiol group may be in the form of disulfide said amino acid and / or said peptide respectively . In yet embodiment, the cofactor is NADPH oxidized form

(NADP +) or reduced form (NADPH, H +).

[0063] More particularly, said mixture comprises:

• a disulfide of formula feed-R '

• a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

• a catalytic amount of reductase enzyme corresponding to said amino acid carrying a thiol group or thiol group in said peptide, and

• a catalytic amount of NADPH

where R and R 'are as defined above.

[0064] the invention will be better understood with the following non-limiting examples in relation to the scope of the invention. All tests listed below were performed under anaerobic conditions.

EXAMPLE 1

[0065] In a reactor containing 150 ml of aqueous solution buffered to pH 7.8, are introduced 10 mL of enzyme glutathione complex. The enzyme complex solution contains: 185 mg (0.6 mmol) of glutathione, 200 U of glutathione reductase, 50 mg (0.06 mmol) of NADPH and 200 U hydrogen dehydrogenase enzyme. The reaction medium is brought to 35 ° C with mechanical stirring. A first transaction is made t = 0. Thereafter, the dimethyl disulfide (9.4 g, 0.1 mol) was placed in a buret and added dropwise into the reactor. At the same time, a hydrogen flow of 4 L h -1(Measured under normal conditions of temperature and pressure) is introduced by bubbling into the reactor. The reaction is carried out at atmospheric pressure. An analysis by gas chromatography of gas leaving the reactor shows almost essentially the presence of hydrogen and methyl mercaptan (traces of water). These output gases are trapped in sodium hydroxide (sodium hydroxide) at 20% in water. DMDS and hydrogen (molar ratio hydrogen / DMDS on the entire reaction = 10.7) is added in 6 hours and the reaction was monitored by potentiometric assay argentometry sodium salt of methylmercaptan in the trap reactor outlet. The final analysis shows that DMDS was converted quantitatively methyl mercaptan. Furthermore,

EXAMPLE 2

[0066] To the reaction mixture of Example 1, is reintroduced 9.4 g (0.1 mol) DMDS dropwise in 6 hours, but this time there is introduced a flow rate of 1 Lh ~ 1 hydrogen for 6 hours also (molar ratio hydrogen / DMDS on the entire reaction = 2.7). The monitoring of the reaction is the same manner as in Example 1 after changing to 20% sodium hydroxide solution at the reactor outlet. The analyzes confirm the end of reaction the complete disappearance of DMDS completely converted to methyl mercaptan found in the form of sodium salt in the soda solution. This example shows the robustness of the catalytic system reproducibility and also shows that we can work with molar ratios hydrogen / DMDS that approximate stoichiometry.

Example 3

[0067] A reactor containing 70 mL of aqueous solution buffered to pH 6.8, are introduced 10 mL of the enzyme glutathione complex. The enzyme complex solution contains: 200 mg (0.65 mmol) of glutathione, 500 U of glutathione reductase, 100 mg (0.12 mmol) and 50 U of NADPH dehydrogenase hydrogen. The latter is obtained from microorganism culture (according Biller and colleagues, "Fermentation Hyperthermophiler am Beispiel von Mikroorganismen

Pyrococcus furiosus, "Shaker Verlag, Maastricht / Herzogenrath, 2002) using techniques well known in the art.

[0068] The reaction medium is brought to 35 ° C under mechanical stirring and nitrogen flushing. A first sample is taken at t = 0. Thereafter, 20 g (0.22 mol) of dimethyl disulfide are added using a syringe.

[0069] At the same time, an amount of 4 Lh "1 hydrogen (measured under normal conditions of temperature and pressure) is introduced by bubbling into the reaction medium. The reaction is performed at atmospheric pressure.

[0070] An analysis by gas chromatography of gas leaving the reactor shows almost essentially the presence of hydrogen, nitrogen and methyl (traces of water). These output gases are trapped in sodium hydroxide to 20% by weight in water. DMDS and hydrogen (molar ratio hydrogen / DMDS on the entire reaction = 4.9) are added in 6 hours and the reaction was monitored by potentiometric titration with silver nitrate of the sodium salt of methylmercaptan in the trap reactor outlet.

[0071] The final analysis shows that DMDS was converted quantitatively methyl mercaptan. In addition, a final analysis by gas chromatography of the reaction mixture confirms the absence of DMDS and methyl mercaptan that was removed from the reactor with hydrogen.

CLAIMS

1. A process for preparing a mercaptan of the formula R-SH, comprising the steps of at least:

a) preparing a mixture comprising:

1) a disulphide of formula RSS-R ',

2) a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

3) a catalytic amount of an enzyme catalyzing the reduction of the bridge

disulfide created between two equivalents of said amino acid carrying a thiol group or thiol group of said peptide,

4) a catalytic amount of an enzyme catalyzing the reduction of

hydrogen,

5) a catalytic amount of a cofactor common to both enzymes

catalyzes the reduction and dehydrogenation

b) adding hydrogen with a catalytic amount of enzyme dehydrogenase hydrogen,

c) carrying out the enzymatic reaction,

d) recovering the mercaptan of the formula R-SH and the mercaptan of the formula R'-SH, e) optional separation and optional purification of the mercaptan of the formula R-SH and / or mercaptan of the formula R'-SH.

2. The method of claim 1 comprising at least the steps of:

a ') preparing a mixture comprising:

• a disulfide of formula feed-R '

• a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

• a catalytic amount of reductase enzyme corresponding to said amino acid carrying a thiol group or thiol group in said peptide,

• a catalytic amount of NADPH

b ') adding hydrogen with a catalytic amount of enzyme dehydrogenase hydrogen,

c ') carrying out the enzymatic reaction,

d ') recovering the mercaptan of the formula R-SH and the mercaptan of the formula R'-SH, e') separation and possible purification of the mercaptan of the formula R-SH and the mercaptan of the formula R'-SH.

3. The method of claim 1 or claim 2, wherein R and R ', identical or different, represent independently of one another, a hydrocarbon, linear, branched or cyclic radical having 1 to 20 carbon atoms, said chain being saturated or carrying one or more unsaturations in the form of double (s) or triple (s) link (s), R and R 'may also form, together with the sulfur atoms carrying them a molecule ring having from 4 to 22 atoms, preferably from 5 to 10 atoms.

4. A method according to any preceding claim, wherein the radicals R and R ', identical or different, are selected independently of one another, from alkyl, cycloalkyl, aryl, alkylaryl, arylalkyl, comprising from 1 to 20 carbon atoms, preferably 1 to 12 carbon preferably carbon of 1 to 6 carbon atoms, linear or branched, saturated or unsaturated, and optionally functionalized with one or more functions chosen from the alcohol function, aldehyde, ketone, acid, amide, nitrile, ester or surrogate functions of sulfur, phosphorus, silicon or halogen.

5. A method according to any preceding claim, wherein the disulfide of the formula RSSR 'is dimethyl disulfide.

6. A method according to any preceding claim, wherein the thiol-bearing amino acid or thiol group of carrier peptide is selected from cysteine, homocysteine, glutathione and thioredoxin.

7. A method according to any preceding claim, wherein hydrogen is introduced by bubbling into the reaction medium.

8. A method according to any preceding claim, wherein the pH of the reaction is between 6 and 8.5, preferably between 7.0 and 8.0.

9. A method according to any preceding claim, wherein the molar ratio hydrogen / disulphide is between 0.01 and 100, preferably between 1 and 20 on the entire reaction.

10. Use of an aqueous solution of enzyme complex comprising an amino acid carrying a thiol function or a peptide bearing a thiol functional group, for the synthesis of a mercaptan from a disulfide.

11. A blend comprising:

1) a disulphide of formula RSS-R ',

2) a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

3) a catalytic amount of an enzyme catalyzing the reduction of the bridge

disulfide created between two equivalents of said amino acid carrying a

thiol group or thiol group of said peptide,

4) optionally a catalytic amount of an enzyme catalyzing the reduction of the hydrogen,

5) a catalytic amount of a cofactor common to both enzymes catalyzing the reduction and dehydrogenation,

6) and optionally hydrogen,

where R and R 'are as defined in claim 1.

12. A mixture according to claim 1 1, comprising:

• a disulfide of formula feed-R '

• a catalytic amount of amino acid carrying a thiol group or thiol group to peptide,

• a catalytic amount of reductase enzyme corresponding to said amino acid carrying a thiol group or thiol group in said peptide, and

• a catalytic amount of NADPH

where R and R 'are as defined in claim 1.