A method of biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate

Abstract

This invention belongs to the field of SNAC (sodium 8-(2-hydroxybenzamido)octanoate) synthesis technology, and particularly relates to a method for biosynthesizing SNAC, comprising the following steps: inoculating yeast into a fermentation medium, adding 2-hydroxy-N-octylbenzamide and a salting agent, controlling the pH of the fermentation medium to be alkaline, and carrying out bio-fermentation to synthesize the SNAC; wherein the yeast is selected from one of *Candida tropicalis*, *Candida maltose*, and *Yarrowia lipolyticis*. This invention organically integrates biological and chemical methods, giving full play to the advantages of both, and innovatively opens up a completely new SNAC synthesis route mainly relying on microbial fermentation. It utilizes microbial cell factories to achieve green synthesis of SNAC, which is beneficial for significantly shortening the SNAC synthesis route. It has advantages such as inexpensive and readily available raw materials, low cost, mild reaction conditions, minimal environmental pollution, high atom economy, and green production.

Description

Technical Field

[0001] This invention relates to the field of sodium 8-(2-hydroxybenzamido)octanoate synthesis technology, and particularly to a method for the biosynthesis of sodium 8-(2-hydroxybenzamido)octanoate. Background Technology

[0002] 8-(2-hydroxybenzamido)octanoate sodium (SNAC) is a non-covalent complexing agent based on the salicylic acid structure. Its amphiphilic molecular design enhances the lipophilicity of drugs and provides local pH regulation and protection. SNAC forms non-covalent complexes with target drugs (such as peptides and polysaccharides), masking their hydrophilic groups and thus improving drug absorption in gastrointestinal epithelial cells. This effectively addresses absorption barriers of oral peptide drugs, and is particularly suitable for gastrointestinal diseases caused by malabsorption of diphosphate compounds. Furthermore, SNAC has significant safety advantages; no mucosal damage or long-term toxicity has been observed clinically, overcoming the toxic side effects bottleneck of traditional absorption enhancers. SNAC has been successfully commercialized in multiple fields and has broad market prospects, for example, as a key excipient (absorption enhancer) for oral semaglutide tablets.

[0003] Currently, the main methods for synthesizing sodium 8-(2-hydroxybenzamido)octanoate include: (1) using salicylamide as the key raw material, reacting it with N'N-carbonyldiimidazole or ethyl chloroformate to generate the intermediate 2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Carsalam), which then undergoes a nucleophilic substitution reaction with ethyl 8-bromooctanoate to obtain ethyl 8-(2,4-dicarbonyl-2H-benzo[e][1,3]oxazine-3(4H)-yl)octanoate, which is then hydrolyzed to obtain 8-(2-hydroxybenzamido)octanoic acid, and finally undergoes a salt formation reaction to obtain the final product SNAC. Among these, ethyl chloroformate is highly toxic and has genotoxic properties, posing a significant risk to human health and environmental pollution. N'N-carbonyldiimidazole, on the other hand, generates wastewater containing imidazole, which is difficult to treat and greatly increases production costs. Furthermore, the liquid-phase retention times of Carsalam and salicylamide are essentially the same, making it difficult to separate and monitor the first-step intermediate and salicylamide. Moreover, the hydrolysis of the second-step intermediate, ethyl 8-(2,4-dicarbonyl-2H-benzo[e][1,3]oxazine-3(4H)-yl)octanoate, uses a strong base, which can cause side reactions and impurity formation. Regarding the aforementioned technology, some researchers (patent CN112661662A) have used oxalyl chloride to react with salicylamide to generate Carsalam; however, oxalyl chloride is a highly toxic, corrosive, and irritating raw material, posing a high safety risk. Another researcher (patent CN112898220A) attempted to circumvent the use of highly toxic raw materials by reacting acetone and / or 2,2-dimethoxypropane as protecting agents with salicylamide to produce 2,2-dimethyl-2,3-dihydro-4H-benzo[1,3]oxazin-4-one, which was then reacted with ethyl 8-bromooctanoate. SNAC was then produced through hydrolysis and salt formation. However, this method is cumbersome, involves a long route, and includes protection and deprotection steps, which can easily lead to significant yield losses of the target product. (2) Using 8-aminooctanoic acid as the key raw material, it reacts with methyl salicylate via an amidation reaction to generate 8-(2-hydroxybenzamido)octanoic acid (patent CN113861062A). Alternatively, using an 8-aminooctanoic acid derivative as the key raw material, such as salicylic acid condensed with ethyl 8-aminooctanoate hydrochloride in the presence of carbonyl diimidazole (CDI), followed by alkaline hydrolysis to obtain 8-(2-hydroxybenzamido)octanoic acid, and finally preparing SNAC via a salt formation reaction (patent CN111978193A). Although the aforementioned methods improve the yield and shorten the reaction route, the synthesis process of the key raw material 8-aminooctanoic acid and its derivatives is complex, and the raw material price is high, resulting in high overall production costs and making it difficult to apply on a large scale. In addition, the condensation reaction requires the addition of an additional condensing agent, which increases the difficulty of product purification. Therefore, it is of great significance to provide a new, green, economical, and readily available SNAC synthesis method suitable for large-scale industrial production. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention takes a novel approach, altering the traditional chemical synthesis model of SNAC by organically integrating biological and chemical methods. It utilizes microbial cell factories to achieve green synthesis of SNAC, significantly shortening the synthesis route (comprising only two key steps). This method offers advantages such as readily available and inexpensive raw materials, lower costs, mild reaction conditions, minimal environmental pollution, and high atom economy and green production. Specifically, this invention is achieved through the following technical solution:

[0005] This invention provides a method for the biosynthesis of sodium 8-(2-hydroxybenzamido)octanoate, comprising the following steps:

[0006] Yeast was inoculated into a fermentation medium, and 2-hydroxy-N-octylbenzamide and a salt-forming agent were added. The pH of the fermentation medium was controlled to be alkaline, and the 8-(2-hydroxybenzamide)octanoic acid sodium salt was synthesized by bio-fermentation.

[0007] The yeast is selected from one of Candida tropicalis, Candida maltose, and Candida lipolytica.

[0008] Furthermore, the fermentation medium also includes a co-solvent, which is selected from one of Triton X-100, Tween 80, Tween 60, nonylphenol polyoxyethylene ether-40, poloxamer 18, dimethyl sulfoxide, and cyclodextrin, and the amount of the co-solvent added is 1-5%. Even further, the co-solvent is selected from Triton X-100 or Tween 80, and the amount added is 0.5%.

[0009] Furthermore, the salt-forming agent is selected from one of NaOH, Na2CO3, or NaHCO3.

[0010] Furthermore, the fermentation medium comprises 100 g / L glycerol, 13 g / L amino-free yeast nitrogen source, 6 g / L yeast extract, 3.64 g / L KH₂PO₄, and 3 g / L K₂HPO₄, and the bio-fermentation is carried out at 25℃-35℃ and 150-250 rpm. Even further, the bio-fermentation is carried out at 28℃-30℃ and 200-250 rpm for 24-72 h.

[0011] Furthermore, the inoculum size of the yeast is 0.5-5%. Even further, the inoculum size is 1%.

[0012] Furthermore, the concentration of the 2-hydroxy-N-octylbenzamide is 20 mM.

[0013] Furthermore, the preparation method of the 2-hydroxy-N-octylbenzamide includes the following steps:

[0014] Methyl salicylate and n-octylamine were mixed evenly and subjected to an amidation reaction. The reaction mixture was collected and purified to obtain the 2-hydroxy-N-octylbenzamide.

[0015] Furthermore, the conditions for the amidation reaction include stirring at 140°C for 16 hours.

[0016] The advantages and positive effects of this invention are as follows:

[0017] This invention organically integrates biological and chemical methods, fully leveraging the advantages of each, and innovatively pioneers a novel synthetic route for sodium 8-(2-hydroxybenzamido)octanoate (SNAC) that primarily relies on microbial fermentation. In this synthetic route, 2-hydroxy-N-octylbenzamide, a substrate for yeast cell factory fermentation, is first synthesized in a single chemical step. Specifically, readily available and inexpensive methyl salicylate and octylamine are used as raw materials to synthesize 2-hydroxy-N-octylbenzamide via an amidation reaction. Then, yeast bio-fermentation is used to convert the 2-hydroxy-N-octylbenzamide substrate. During bio-fermentation, the substrate can be selectively oxidized to 8-(2-hydroxybenzamido)octanoic acid and its salt can be formed simultaneously, yielding SNAC. This significantly shortens the SNAC synthetic route and offers advantages such as readily available and inexpensive raw materials, low cost, mild reaction conditions, minimal environmental pollution, high atom economy, and green production, making it potential for large-scale industrial production. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 This is a route diagram for the synthesis of sodium 8-(2-hydroxybenzamido)octanoate using yeast bio-fermentation, as described in an embodiment of the present invention.

[0020] Figure 2 This is a thin-layer chromatography result of the synthesis of sodium 8-(2-hydroxybenzamido)octanoate by bio-fermentation of Candida tropicalis in an embodiment of the present invention;

[0021] Figure 3 This is a thin-layer chromatography result of the synthesis of sodium 8-(2-hydroxybenzamido)octanoate by bio-fermentation of Candida maltose in an embodiment of the present invention;

[0022] Figure 4This is a thin-layer chromatography result of the synthesis of sodium 8-(2-hydroxybenzamido)octanoate by bio-fermentation of Yeast lipolytica in an embodiment of the present invention. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The embodiments described herein are for illustrative purposes only and are not intended to limit the invention.

[0024] Based on the information contained herein, various changes to the precise description of the invention can be readily made by those skilled in the art without departing from the spirit and scope of the appended claims. It should be understood that the scope of the invention is not limited to the defined processes, properties, or components, as these embodiments and other descriptions are merely illustrative of specific aspects of the invention. In fact, various modifications to embodiments of the invention that will be apparent to those skilled in the art or related fields are covered within the scope of the appended claims.

[0025] To better understand the invention and not to limit its scope, all figures and other numerical values ​​used in this invention to indicate amounts, percentages, or other quantities should, in all cases, be understood to be modified by the word "approximately." Therefore, unless specifically stated otherwise, the numerical parameters listed in the specification and appended claims are approximate values ​​and may vary depending on the desired properties being sought. Each numerical parameter should at least be considered as obtained based on reported significant figures and through conventional rounding methods. Furthermore, the terms "comprising," "including," "containing," "having," and similar words are non-limiting in meaning, allowing for the addition of other steps and components that do not affect the result.

[0026] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0027] This invention, through screening, obtained a class of microbial strains for the biosynthesis of SNAC. These strains typically possess multiple ω-oxidases (such as CYP52, FAO, ADH, and FALDH), endowing them with strong ω-oxidation capabilities—the ability to oxidize terminal long-chain alkyl groups of compounds to carboxyl groups. This allows them to synthesize the artificially synthesized compound 2-hydroxy-N-octylbenzamide into 8-(2-hydroxybenzamido)octanoic acid, which further undergoes a salt-forming reaction with sodium hydroxide or sodium bicarbonate to obtain sodium 8-(2-hydroxybenzamido)octanoate (SNAC). This invention offers a novel approach, altering the traditional chemical synthesis model of SNAC by organically integrating biological and chemical methods, enabling the green synthesis of SNAC using microbial cell factories. Specifically, the method first synthesizes 2-hydroxy-N-octylbenzamide, a substrate for yeast cell factory fermentation, in one step using a chemical method. Then, the 2-hydroxy-N-octylbenzamide substrate is converted in a yeast cell factory, achieving simultaneous selective oxidation and salt formation of the substrate. This greatly shortens the synthetic route of SNAC and has advantages such as cheap and readily available raw materials, low cost, mild reaction conditions, minimal environmental pollution, high atom economy, and green production, making it a potential candidate for large-scale industrial production.

[0028] Based on this, embodiments of the present invention provide a method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate (SNAC), comprising the following steps:

[0029] Yeast was inoculated into a fermentation medium, and 2-hydroxy-N-octylbenzamide and a salt-forming agent were added. The pH of the fermentation medium was controlled to be alkaline, and the 8-(2-hydroxybenzamide)octanoic acid sodium salt was synthesized by bio-fermentation.

[0030] The yeast is selected from one of Candida tropicalis, Candida maltosa, and Yarrowia lipolytica.

[0031] Optionally, the fermentation medium further includes a solubilizer, which includes, but is not limited to: Triton X-100, Tween 80, Tween 60, nonylphenol polyoxyethylene ether-40 (NP-40), poloxamer 188 (P188), dimethyl sulfoxide (DMSO), or cyclodextrin. Triton X-100 or Tween 80 is preferred.

[0032] Optionally, the amount of the co-solvent added is 1-5% (w / v or v / v); that is, when the co-solvent is solid (NP40 and P188), the amount of the co-solvent added accounts for 1-5% (w / v) of the fermentation medium by mass-volume ratio, and when it is liquid (Triton X-100, Tween 80), the amount of the co-solvent added accounts for 1-5% (v / v) of the total volume of the fermentation medium by volume ratio; preferably 0.5%.

[0033] The fermentation medium used to cultivate the yeast is a conventional liquid culture medium in the art. In a preferred embodiment of the present invention, the fermentation medium comprises 100 g / L glycerol, 13 g / L amino-free yeast nitrogen source, 6 g / L yeast extract, 3.64 g / L KH2PO4, and 3 g / L K2HPO4.

[0034] Optionally, the salt-forming agent is selected from NaOH, Na2CO3, or NaHCO3. By adding the salt-forming agent and controlling the pH value to 7-8 during the reaction, a neutralization reaction occurs to generate the corresponding sodium salt SNAC.

[0035] The culture conditions used are standard yeast culture conditions, such as 25℃-35℃ and 150-250 rpm. The culture time is adjusted adaptively according to cell activity, inoculum size, substrate concentration, and conversion rate, and is usually 24-72 hours.

[0036] Preferably, the culture conditions are 28℃-30℃ and 200-250 rpm, more preferably 30℃ and 250 rpm.

[0037] Optionally, the amount of yeast inoculated is 0.5-5%, preferably 1%.

[0038] Optionally, the concentration of the 2-hydroxy-N-octylbenzamide is 20 mM.

[0039] The method for purifying SNAC from fermentation medium adopts conventional methods in the art, such as cooling the fermentation broth (0-4°C) to crystallize, filtering to obtain SNAC solid, washing with an alcohol solution (such as isopropanol), and recrystallizing to obtain high-purity SNAC. The present invention does not have any special limitations on these methods and steps.

[0040] 2-Hydroxy-N-octylbenzamide, a substrate for yeast fermentation, can be synthesized using conventional methods in the art, for example, by esterification of salicylic acid (CAS No.: 69-72-7) with n-octylamine (CAS No.: 111-86-4); or by acylation of methyl salicylate (CAS No.: 119-36-8) or salicyl chloride (CAS No.: 1441-87-8) with n-octylamine (CAS No.: 111-86-4). Esterification and amidation reactions are conventional techniques in the art and will not be described in detail here.

[0041] The raw materials used in this invention for synthesizing 2-hydroxy-N-octylbenzamide are inexpensive and readily available, thus avoiding the use of expensive 8-aminooctanoic acid or its derivatives, as well as toxic ethyl chloroformate and other raw materials. The subsequent bio-fermentation conversion of 2-hydroxy-N-octylbenzamide is carried out under mild and easily controllable reaction conditions, giving it the advantages of high atom economy and green production.

[0042] In a preferred embodiment, the preparation method of the 2-hydroxy-N-octylbenzamide includes the following steps:

[0043] Methyl salicylate and n-octylamine were mixed evenly and subjected to an amidation reaction. The reaction mixture was collected and purified to obtain the 2-hydroxy-N-octylbenzamide.

[0044] It is understood that each molecule of methyl salicylate and each molecule of n-octylamine undergoes an amidation reaction. Therefore, a molar ratio of methyl salicylate to n-octylamine of 1:1 is preferred to ensure sufficient reaction between the raw materials. Of course, to improve reaction efficiency, one of the raw materials can be appropriately in excess, such as a molar ratio of methyl salicylate to n-octylamine of 1:1.1.

[0045] Optionally, the conditions for the amidation reaction include stirring at 140°C for 16 hours.

[0046] Optionally, the method for purifying the 2-hydroxy-N-octylbenzamide includes: collecting the reaction mixture, cooling it to room temperature, diluting it with dichloromethane in a volume of 10-20 times that of the reaction mixture, washing it twice with 5% hydrochloric acid aqueous solution, then washing it once with distilled water, collecting the organic phase, drying it with anhydrous sodium sulfate, filtering it, concentrating it by rotary evaporation, and purifying it by silica gel column chromatography to obtain 2-hydroxy-N-octylbenzamide solid.

[0047] The present invention will be further illustrated below with reference to specific embodiments. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions, such as those described in *Molecular Cloning: A Laboratory Manual (Fourth Edition)* published by Cold Spring Harbor Laboratory, or generally under the conditions recommended by the manufacturer.

[0048] The formulations of the main culture media involved in the following examples are as follows:

[0049] (1) YPD medium: 10 g / L yeast extract, 20 g / L peptone and 20 g / L glucose;

[0050] (2) Fermentation medium: 100 g / L glycerol, 13 g / L amino-free yeast nitrogen source, 6 g / L yeast extract, 3.64 g / L KH2PO4 and 3 g / L K2HPO4.

[0051] Add 20 g / L of agar to the solid culture medium.

[0052] The microbial strains (Candida tropicalis and Candida maltose) involved in the following examples were purchased from the China Center for Type Culture Collection, and Yeastra lipolytica po1f was commercially available.

[0053] 1. Chemical synthesis of 2-hydroxy-N-octylbenzamide

[0054] 1.29 mL of methyl salicylate (10 mmol, 1.0 eq.) and 1.65 mL of n-octylamine (10 mmol, 1.0 eq.) were added to a 50 mL single-necked reaction flask. The reaction mixture was stirred at 140°C for 16 hours. TLC analysis showed that the methyl salicylate was completely consumed, and the developing solvent was PE / EA = 15 / 1. After the reaction was complete, the reaction mixture was cooled to room temperature and diluted with 50 mL of dichloromethane. The solution was washed twice with 5% hydrochloric acid aqueous solution (2 × 10 mL), and then washed with distilled water (10 mL). The organic phase was dried over anhydrous sodium sulfate (Na2SO4), filtered, concentrated by rotary evaporation, and purified by silica gel column chromatography (PE / EA = 30 / 1 to 20 / 1) to give 1.99 g of 2-hydroxy-N-octylbenzamide as a white solid.

[0055] The reaction equation for this step is as follows:

[0056] .

[0057] The obtained 2-hydroxy-N-octylbenzamide white solid was analyzed by 1H and 1C NMR spectroscopy. Spectra were recorded on a Bruker AV-400 spectrometer using deuterated chloroform (CDCl3) as solvent. For 1H NMR spectra, chemical shifts were reported in ppm, with the internal standard chloroform signal at 7.26 ppm as the standard. For 13C NMR spectra, chemical shifts were reported in ppm, with the internal standard chloroform signal at 77.16 ppm as the standard. Data reporting: s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet, td = three sets of doublets, m = multipeak or unresolved, coupling constant in Hz, integral.

[0058] The 1H NMR spectrum of 2-hydroxy-N-octylbenzamide is as follows: 1 ¹H NMR (400 MHz, CDCl₃) δ 12.40 (s, 1H), 7.41 – 7.36 (m, 1H), 7.33 (dd, J = 7.9, 1.6 Hz, 1H), 6.98 (dd, J = 8.4, 1.2 Hz, 1H), 6.86 – 6.81 (m, 1H), 6.31 (s, 1H), 3.44 (td, J = 7.2, 5.7 Hz, 2H), 1.67 – 1.57 (m, 2H), 1.43 – 1.20 (m, 10H), 0.88 (t, J = 7.1 Hz, 3H). The carbon NMR spectrum is as follows: 13 C NMR (101 MHz, CDCl3) δ 170.0, 161.7, 134.2, 125.3,118.8, 118.7, 114.5, 39.9, 31.9, 29.6, 29.4, 29.3, 27.1, 22.8, 14.2.

[0059] 2. Yeast conversion of 2-hydroxy-N-octylbenzamide to synthesize SNAC

[0060] Seed culture: Activate the yeast strain by streaking it onto YPD solid medium and incubate at 28℃ for 2-3 days. Then, pick a single colony and inoculate it into a test tube containing 2 mL of YPD liquid medium. After overnight incubation, inoculate 1% of the colony into a 100 mL shake flask containing 20 mL of YPD liquid medium. Incubate for 1-2 days, then centrifuge to collect the bacteria.

[0061] Yeast transformation experiment: The cell pellet was resuspended in 20 mL of fermentation medium, followed by the addition of 20 mM 2-hydroxy-N-octylbenzamide substrate and 0.5% co-solvent. The reaction was carried out at 30 °C and 250 rpm for 48 h on a shaker. During the reaction, the pH was adjusted to 8.0 using NaOH or NaHCO3 solution.

[0062] After the reaction, samples were taken and analyzed using thin-layer chromatography (TLC). The TLC procedure for SNAC detection is as follows: Take 500 μL of sample, add an equal volume of ethyl acetate and 50 μL of 4M HCl, shake thoroughly to mix, and centrifuge at 12000 rpm for 2 min. Transfer the supernatant to another clean 1.5 mL EP tube, and spot the sample onto a silica gel plate using a capillary tube. The developing solvent is PE / EA = 2:1 (v:v), with the addition of 5% formic acid.

[0063] The yeast strains used in this embodiment include *Candida tropicalis* (accession number: CCTCC AY 2018001), *Candida maltosa* (accession number: CCTCC AY 93023), and *Yarrowia lipolytica* po1f (accession number: ATCC MYA-2613). The cosolvent used for *Candida tropicalis* CCTCC AY 2018001 and *Yarrowia lipolytica* po1f was 0.5% (v / v) Triton X-100, while the cosolvent used for *Candida maltosa* CCTCC AY 93023 was 0.5% (v / v) Tween 80.

[0064] Figure 2-4 TLC chromatography results of the fermentation broths of *Candida tropicalis* CCTCC AY 2018001, *Candida maltose* CCTCC AY 93023, and *Yersinia lipolytica* po1f are shown. Lane S represents the substrate 2-hydroxy-N-octylbenzamide, lane P represents SNAC standard, and lanes CT, CM, and YL represent the fermentation products of *Candida tropicalis* CCTCC AY 2018001, *Candida maltose* CCTCC AY 93023, and *Yersinia lipolytica* po1f, respectively. It is evident that SNAC was successfully synthesized in the fermentation culture broth.

[0065] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method of biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate, characterized by, Includes the following steps: Yeast was inoculated into a fermentation medium, and 2-hydroxy-N-octylbenzamide and a salt-forming agent were added. The pH of the fermentation medium was controlled to be alkaline, and the 8-(2-hydroxybenzamide)octanoic acid sodium salt was synthesized by bio-fermentation. The yeast is selected from one of Candida tropicalis, Candida maltose, and Candida lipolytica.

2. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 1, characterized in that, The fermentation medium also includes 1-5% co-solvent, which is selected from one of Triton X-100, Tween 80, Tween 60, nonylphenol polyoxyethylene ether-40, poloxamer 18, dimethyl sulfoxide and cyclodextrin.

3. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 2, characterized in that, The cosolvent is Triton X-100 or Tween 80, and the amount added is 0.5% by volume.

4. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 1, characterized in that, The fermentation medium comprises 100 g / L glycerol, 13 g / L amino-free yeast nitrogen source, 6 g / L yeast extract, 3.64 g / L KH2PO4 and 3 g / L K2HPO4.

5. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 1, characterized in that, Biological fermentation was carried out at 25℃-35℃ and 150-250rpm for 24-72h.

6. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 1, characterized in that, The inoculation amount of the yeast is 0.5-5%.

7. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 1, characterized in that, The concentration of the 2-hydroxy-N-octylbenzamide is 20 mM.

8. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 1, characterized in that, The salt-forming agent is selected from one of NaOH, Na2CO3 or NaHCO3.

9. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 3, characterized in that, The preparation method of the 2-hydroxy-N-octylbenzamide includes the following steps: Methyl salicylate and n-octylamine were mixed evenly and subjected to an amidation reaction. The reaction mixture was collected and purified to obtain the 2-hydroxy-N-octylbenzamide.

10. The method for biosynthesizing sodium 8-(2-hydroxybenzamido)octanoate according to claim 9, characterized in that, The conditions for the amidation reaction included stirring at 140°C for 16 hours.

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