16/2/25


Natural vanillin

Background




Vanillin , is known under the chemical name 4-hydroxy-3-methoxybenzaldehyde, which is present in vanilla beans, is one of the most widely used aromatic compounds. The perfume composition is widely used in the fields of foods, beverages, perfumes, cosmetics, intermediates in agriculture, chemical industry, pharmaceutical industry and the like. It was predicted that in 2025, the market demand for vanillin would exceed 59000 tons. The vanillin sold in the market at present is mainly produced by a chemical method, and the vanillin is synthesized by eugenol, guaiacol and the like.

The biotechnological process offers a promising alternative due to the inherently mild reaction conditions and the use of renewable raw materials. In addition, according to the united states and european food regulations, biologically produced vanillin is known as natural vanillin.





Natural vanillin from ferulic acid

Ferulic aci is produced from   maize peels , rice bran ,wheat......(more info here)
 

vanillin

Since 1990 , several patent applications have been filed concerning the microbial or enzymatic production of vanillin. In general, a suitable precursor is transformed to vanillin by a microorganism or an enzyme. Suggested precursors are eugenol, isoeugenol, ferulic acid, curcumin or benzoe siam resins. Usually, transformation yields are extremely low.
Examples are e.g. Haarman & Reimer (EP 0 405 197 Al) claiming a production of 18 m L"^ starting from 0.2 gL"-'- eugenol using the microorganisms Serratia, Klebsiella or Enterobacter. This transformation furthermore takes 13 days. Pernod-Ricard (EP 453 368 A) claim 46 mgL-1 vanillin obtained in a δ days Pycnoporus fermentation from ferulic acid. In Mey/So 24.4.98 this line is also Kraft General Foods (US 5,128,253) claiming 210 mgL'1 vanillin from ferulic acid within 54 days. In order to obtain this titer a reducing agent had to be added as otherwise the formation of vanillin would not occur and only vanillic acid would be formed. Takasago ( JP 227980/1993) prepared mutants of Pseudomonas strains that are blocked in the degradation pathway of vanillin. Thus, starting with 1 gL"* ferulic acid 0.28 L~* vanillin could be obtained.

Since then a lot of research has been made  and productivity and yield are increased  as it can be seen in the numerous patents taken , some of themshown hereafter

A selected microorganism is multiplied in a fermenter. When the population is sufficient, ferulic acid is introduced, usually in several additions. It is then converted into vanillin, with the vanillin/ferulic acid conversion yield reaching up to 80%. The fermentation broth is then filtered and extracted with an appropriate solvent. The vanillin is then purified  generally by crystallization.




vanillin  ferulic




IL124800A 1998-06-08  Application filed by Givaudan Roure Int


Example 1 250 mL shake flasks containing 50 mL of the following medium were prepared: 103 gL"1 sucrose, 4 gL"1 Na2HP04, 1 gL'1 KH2PO4, 1 gL-1 yeast extract, 0.2 gL'1 NaCl, 0.2 gL"1 MgS04 and 0.05 gL"1 CaCl2. The pH was adjusted to 7.2 using NaOH. A shake flask was inoculated with 2 mL of preculture of Streptomyces setonii ATCC 39116 and cultivated at 37°C, 190 rpm for 16 hours. At the end of the growth phase 0.3 g ferulic acid (purchased from Aldrich, cat. no. 12.870-8, 99%) was added to the culture. For this - 8 -purpose a 10 % w/w solution of the acid substrate in 0.5 M NaOH (final pH of the solution was approximately 7.2) was previously prepared and sterile-filtered. The flask was incubated again at 37°C, 190 rpm. After 31.5 hours of biotransformation (incubation) a vanillin concentration of 3.10 L"l (HPLC) was reached. A molecular yield of 66 mol % was calculated.

  DE19532317A1   1995-09-01   Haarmann & Reimer Gmbh

Example 3  Production of vanillin in a 10 l fermenter
5 l culture medium (4 g / l glucose, 10 g / l malt extract and 6 g / l yeast extract) were sterilized in a fermenter and after cooling with 100 ml of a Pre-culture of DSM 9992 inoculated according to Example 1.
The culture conditions were: 37 ° C, 500 rpm, 5 l air / min. 12.5 hours after 1.634 kg of an approximately 3.7% ferulic acid solution (60.2 g Ferulic acid) added. After 17.5 hours over a period of 10 Hours another 4.377 kg of an approximately 3.7% ferulic acid solution (164.72 g Ferula acid) pumped in.
The fermentation was stopped after 32 hours. The concentration on Vanillin was 11.5 g / l and 1 g / l of unreacted ferulic acid was still present. The final volume was 11.29 l. This is an implementation of 77.8% of theory based on converted ferulic acid.



Natural vanillin
from isoeugenol



vanillin

WO-2022133274-A1    Biosynthesis of vanillin from isoeugenol     Basf Se, Basf Corporation    Rui Zhou, Junying MA, Oliver YU    2020-12-18    2021-12-17    2022-06-23                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
WO-2022133274-A1    Biosynthesis of vanillin from isoeugenol     Basf Se, Basf Corporation     2020-12-18      2022-06-23    


BACKGROUND OF THE INVENTION
Vanilla flavors are among some of the most frequently used flavors worldwide. They are used in the flavorings of numerous foods such as ice cream, dairy products, desserts, confectionary, bakery products and spirits. They are also used in perfumes, pharmaceuticals and personal hygiene products.

 Natural vanilla flavor has been obtained traditionally from the fermented pods of vanilla orchids. It is formed mainly after the harvest during several weeks of a drying and fermentation process of the beans by hydrolysis of vanillin glucoside that is present in the beans. The essential aromatic substance of vanilla flavor is vanillin (4-hydroxy 3- methoxybenzaldehy de) .

 Vanillin is one of the most common flavor chemicals and is widely used in the food and beverage, perfume, pharmaceutical, and medical industries. About 12,000 tons of vanillin is consumed annually, of which only 20-50 tons are extracted from vanilla beans, the rest is produced synthetically, mostly from petrochemicals such as guaiacol and lignin. In recent years, increasing demands for natural flavors have led the flavor industry to produce vanillin by bioconversion, as the products of such bioconversion are considered natural by various regulatory and legislative authorities (e.g., European Community Legislation) when produced from biological sources such as living cells or their enzymes, and can be marketed as “natural products”.


Natural isoeugenol can be extracted from essential oils and is economical to use for the production of vanillin by enzymatic conversion or microbial bioconversion. Vanillin production via conversion of isoeugenol has been widely reported in a number of microorganisms, including Aspergillus niger, Bacillus subtilis, and Pseudomonas putida.

However, the reported titers produced by these microorganisms were very low (less than 2 g/L), significantly limiting the practical application of this approach in the industry. Moreover, the reported bioconversion processes were complicated, further increasing the cost of vanillin production.
 Accordingly, there is a need in the art for more cost-effective methods for producing vanillin with higher titers and conversion rates.

Example 6: Bioconversion of isoeugenol to vanillin in fermenter
 A fermentation process was developed for the bioconversion of isoeugenol to vanillin using the E. coli strain ISEG-V224 in fermenters. One ml of glycerol stock of ISEG-V224 was inoculated into 100 mL seed culture medium (Luria-Bertani medium with 5g/L yeast extract, lOg/L tryptone, lOg/L NaCl, and 50mg/L kanamycin) in 500 mL flasks. The seed was cultivated in a shaker with shaking speed of 200rpm at 37 °C for 8 hours and then transferred into 2 liter of fermentation medium of Luria-Bertani medium plus 6 g/L initial glucose, 50mg/L kanamycin in a 5 -liter fermenter.
 The present fermentation process has two phases; namely, a cell growth phase and a bioconversion phase. The cell growth phase was from 0 hour to 17 hours and is referred as elapsed fermentation time (EFT). During EFT, the fermentation parameters were set as follows: Air flow: 0.6vvm; pH was controlled not to go below 7.1 by using 4N NaOH. The growth temperature was set to 30°C and the agitation speed was set to 300-500 rpm. The level of dissolved oxygen (DO) was maintained above 30%. At EFT 6.5h, IPTG was added to a final concentration of 0.5mM and glucose was fed at a rate of 0.4 g/L/hour for 17 hours.

The bioconversion phase was from EFT 17 hour to 46.5 hour. The fermentation parameters were set as follows: Air flow: 0.4vvm. pH was controlled not to go below 8.0 with 4N NaOH, and the temperature was kept at 30°C. Agitation was set to 250-500 rpm and DO was maintained above 30%. The feeding of isoeugenol at a rate of 1.5 g/L began at EFT 17 hour and continued for 4 hours. At EFT 21 hours, the isoeugenol feeding rate was reduced to 1 g/L. At EFT 23 hours, the isoeugenol feeding rate was further reduced to 0.6 g/L/hour and maintained for another 8 hours. Samples were collected at specific time intervals, then analyzed by HPLC as described in Example 4. [00126] Referring to FIG. 6, using a 5-liter fermenter, the E. coli strain ISEG-V224 which was transformed with the UmlEM gene was able to produce vanillin using isoeugenol as the substrate at a titer as high as 14.8 g/L. It is also worth noting that the molar conversion rate from isoeugenol to vanillin reaches above 90%.
                                                                                                                                                                                                                                                               

Vanillin from wood

from US4021493A (1975)   Current Assignee    TABERT Inc     Medicorp Research Laboratories Corp


from US4021493A (1975)


It is known that vanillin can be made by oxidizing a lignin or lignosulfonate material, such as results from the kraft and sulfite cooking processes for producing pulp. The oxidation is carried out at elevated temperatures and pressures in the presence of an oxygen-containing gas in an alkaline solution. The resulting alkaline aqueous solution contains in addition to the desired vanillin, the unwanted contaminants, such as orthovanillin, acetovanillone, para-hydroxybenzaldehyde and syringaldehyde, which must be removed from the vanillin if the vanillin is to be of high purity and quality.
Numerous processes have been proposed for purifying vanillin from alkaline solutions. These include Sandborn U.S. Pat. No. 2,104,701. This patent treats by countercurrent extraction the aqueous alkaline solution of vanillin with a suitable water-immiscible solvent, such as normal butyl alcohol, and recovers the solvent for reuse. The vanillin is removed from the solvent and is subjected to further purification by any known means, such as by distilling the solvent as its water-binary mixture to leave the vanillin compound in an alkaline aqueous solution for further refining.
Other patents employing butyl alcohol extractions include U.S. Pat. Nos. 2,399,607, 2,104,701 and 2,489,200. Other patents employ propyl alcohol or isopropyl alcohol as the extractant, such as U.S. Pat. No. 2,721,221.
Other patents disclosed purification of vanillin by employing distillation treatments such as U.S. Pat. Nos. 2,506,540 and 2,745,796.
While the foregoing treatments are useful in purifying vanillin, it is desired to provide improved processes which more efficiently and effectively isolate and separate vanillin from its chemically related contaminating impurities. Accordingly, it is an object of the present invention to provide an efficient and effective process for removing and purifying vanillin from aqueous alkaline solutions containing contaminants.
vanillin





Some more patents  related to vanillin by biotransformation  and its purification


CN117904216A    2024-01-23 Method for improving vanillin yield    Current Assignee     Tianjin University Advanced Research Institute Of Synthetic Biology


US20240158329A1 (2021) Method for purifying vanillin or derivatives thereof obtained by a biotechnological method
Abstract
The present invention relates to a process for purifying a fermentation must (M), obtained via a biotechnological process, comprising biomass and vanillin or derivatives thereof in aqueous solution, for the preparation of a crystallized vanillin or derivatives thereof, characterized in that, throughout the purification process, the vanillin or derivatives thereof in protonated or salified form remain in aqueous solution.
 PROCESS FOR PURIFYING VANILLIN BY LIQUID-LIQUID EXTRACTION  FR2984314B1
Abstract translated from French  Worldwide applications  2011 FR 2012

A process for the purification of vanillin, from a solution of vanillin in a solvent S1 containing impurities, is described, comprising the following steps: a) a step of evaporation of the solvent S1 in the presence of water to obtain an aqueous solution vanillin; b) a liquid/liquid extraction step by bringing the aqueous solution obtained at the end of step a) into contact with a solvent S2, at a pH greater than 8 and less than 10, to obtain an organic phase and an aqueous phase containing vanillin and residual solvent S2; c) a step of precipitation, at a pH comprised from 4 to 7.5, of the vanillin contained in the aqueous phase obtained at the end of step b), and d) a step of isolation of the vanillin.
  CN111548260A  *  2020-06-02  2020-08-18  上海欣晨新技术有限公司  Separation method of 6-methyl vanillin and vanillin
Separation method of 6-methyl vanillin and vanillin
Abstract
The invention provides a separation method of vanillin and impurity 6-methyl vanillin, which realizes the good separation of 6-methyl vanillin and vanillin by extracting the mixed solution containing vanillin, 6-methyl vanillin and other impurities with alcohol water; wherein, an appropriate extractant alcohol aqueous solution is selected, and the mass concentration of alcohol in the alcohol aqueous solution is 20-60%; the weight ratio of the solvent for alcohol-water extraction is (0.5-4): 1; furthermore, the method can well realize the effective separation of vanillin, 6-methyl vanillin and other impurities in the vanillin crystallization mother liquor, so that the vanillin finished product obtained in the separation and refining process can meet higher quality requirements, the loss of vanillin in the separation process is reduced, and the yield of vanillin is improved.
  DE19532317A1   1995-09-01  1997-03-06  Haarmann & Reimer Gmbh   Process for the production of vanillin and suitable microorganisms

 Claims (4)  translated from German
1. Amycolatopsis sp. from the genus Pseudonocardia with the in the German Collection for Microorganisms and Cell Cultures GmbH in Braunschweig under the numbers DSM 9991 and DSM 9992 Tribes. 2. Process for the preparation of vanillin from ferulic acid in the presence of Amycolatopsis sp. DSM 9991 or DSM 9992 or its enzymes or of microorganisms with genetic material from Amycolatopsis sp. DSM 9991 or DSM 9992, which are the structural and regulatory genes for the Encodes enzymes that are effective in this reaction. 3. The method according to claim 2, according to which natural as the starting component uses ferulic acid. 4. Use of the produced by the method according to claims 2 and 3 Vanillins for the production of flavors.

Example 3 Production of vanillin in a 10 l fermenter
5 l culture medium (4 g / l glucose, 10 g / l malt extract and 6 g / l yeast extract) were sterilized in a fermenter and after cooling with 100 ml of a Pre-culture of DSM 9992 inoculated according to Example 1.
The culture conditions were: 37 ° C, 500 rpm, 5 l air / min. 12.5 hours after 1.634 kg of an approximately 3.7% ferulic acid solution (60.2 g Ferulic acid) added. After 17.5 hours over a period of 10 Hours another 4.377 kg of an approximately 3.7% ferulic acid solution (164.72 g Ferula acid) pumped in.
The fermentation was stopped after 32 hours. The concentration on Vanillin was 11.5 g / l and 1 g / l of unreacted ferulic acid was still present. The final volume was 11.29 l. This is an implementation of 77.8% of theory based on converted ferulic acid.



Some selected  patents on the same   below

 
US4478747A * 1982-05-11 1984-10-23 Genetics International, Inc. Biologically produced acid precipitable polymeric lignin
DE3920039A1 * 1989-06-20 1991-01-03 Haarmann & Reimer Gmbh METHOD FOR PRODUCING NATURAL VANILLIN
US5128253A * 1991-05-31 1992-07-07 Kraft General Foods, Inc. Bioconversion process for the production of vanillin
US5712132A * 1992-07-24 1998-01-27 V. Mane Fils S.A. Method for the enzymatic preparation of aromatic substances
FR2694020B1 * 1992-07-24 1994-10-14 Mane Fils Sa V Process for the preparation of aromatic substances by enzymatic route.
FR2724394B1 * 1994-09-13 1997-01-10 Agronomique Inst Nat Rech PROCESS FOR OBTAINING VANILLIC ACID AND VANILLIN BY BIOCONVERSION BY A COMBINATION OF FILAMENTOUS MICROORGANISMS
 
DE19649655A1 1996-11-29 1998-06-04 Haarmann & Reimer Gmbh Synthetic enzymes for the production of coniferyl alcohol, coniferyl aldehyde, ferulic acid, vanillin and vanillic acid and their use
CA2238215A1 * 1997-06-19 1998-12-19 Markus Wetli Process for the production of vanillin
DE19960106A1 * 1999-12-14 2001-06-21 Haarmann & Reimer Gmbh Enzymes and genes for the production of vanillin
DE10144308A1 * 2001-09-10 2003-03-27 Haarmann & Reimer Gmbh Genetic modification of Amycolatopsis spp., used in producing vanillin, e.g. from ferulic acid, involves contacting culture with transforming and different DNA, magnesium and cesium chloride and polyethylene glycol
GB0307232D0 2003-03-28 2003-04-30 Zylepsis Ltd Production of vanillin
EP1649029B1 2003-06-19 2014-12-17 Evolva SA A method of producing a low molecular weight plant secondary metabolite in a yeast cell
MXPA06011521A * 2004-04-08 2007-03-21 Astellas Pharma Inc Compound ws 727713.
CN100429317C 2005-06-17 2008-10-29 江南大学 Process for producing vanillic acid and vanillic aldehyde by fermentation transforming bran foots
EP2721148B1 2011-06-17 2018-09-12 Symrise AG Microorganisms and methods for producing substituted phenols
CN102321563B * 2011-10-24 2013-04-03 江南大学 Amycolatopsis sp. and method for preparing vanillin through whole-cell transformation of Amycolatopsis sp.
FR2984314B1 2011-12-15 2014-01-17 Rhodia Operations PROCESS FOR PURIFYING VANILLIN BY LIQUID-LIQUID EXTRACTION
PL2890801T3 * 2012-08-28 2021-11-15 Privi Biotechnologies Pvt. Ltd. Microbial biotransformation of aromatic acids to their reduced carbon aromatic acids
EP2914733A1 * 2012-11-05 2015-09-09 Evolva SA Vanillin synthase
SK9325Y1 2013-01-24 2021-09-29 Rhodia Operations Natural vanillin
EP2772142A1 * 2013-02-27 2014-09-03 Symrise AG Vanillin
WO2014131532A1 2013-02-27 2014-09-04 Symrise Ag Material mixtures containing vanillin and vanillyl vanillate
CN105246868A 2013-05-21 2016-01-13 罗地亚经营管理公司 Optimized process for extraction of ferulic acid with pretreatment
US9932610B2 2013-11-04 2018-04-03 Bgn Tech Llc Methods of making vanillin via the microbial fermentation of ferulic acid from eugenol using a plant dehydrogenase
EP2881469B1 2013-12-03 2017-04-05 Symrise AG Shuttle vectors and expression vectors for Amycolatopsis
WO2015121379A2 * 2014-02-12 2015-08-20 Evolva Sa Methods of improving production of vanillin
EP2963110A1 2014-07-01 2016-01-06 Rhodia Opérations Microorganisms and methods for producing vanillin
CN113755422B * 2021-10-09 2023-03-24 陕西海斯夫生物工程有限公司 Recombinant amycolatopsis capable of highly producing vanillin, construction method 
FR3134583A1 2022-04-15 2023-10-20 Rhodia Operations Continuous process of growth of a microorganism
 
US2745796A 1953-10-21 1956-05-15 Aschaffenburger Zellstoffwerke Method of recovering vanillin
DE1132113B 1959-07-09 1962-06-28 Aschaffenburger Zellstoffwerke Method of purifying vanillin
DE3920039A1 1989-06-20 1991-01-03 Haarmann & Reimer Gmbh METHOD FOR PRODUCING NATURAL VANILLIN
CA2238215A1 1997-06-19 1998-12-19 Markus Wetli Process for the production of vanillin
FR2950886B1 2009-10-02 2011-10-28 Rhodia Operations PROCESS FOR SEPARATING PHENOLIC COMPOUNDS IN SALIVED FORM
MX355785B 2011-08-08 2018-04-30 Int Flavors & Fragrances Inc Compositions and methods for the biosynthesis of vanillin or vanillin beta-d-glucoside.
FR2984314B1 2011-12-15 2014-01-17 Rhodia Operations PROCESS FOR PURIFYING VANILLIN BY LIQUID-LIQUID EXTRACTION
SK9325Y1 2013-01-24 2021-09-29 Rhodia Operations Natural vanillin
CN105132472B * 2015-07-27 2019-01-08 厦门欧米克生物科技有限公司 The purposes of one seed sand streptomycete and the production method of vanillic aldehyde

US2449364A * 1945-10-15 1948-09-14 Hoffmann La Roche Process for isolating vanillin
US4021493A * 1973-11-08 1977-05-03 Canadian International Paper Company Vanillin recovery process
JPS5946497B2 * 1979-12-26 1984-11-13 ボイズ・キヤスケ−ド・コ−ポレ−シヨン Method for separating phenols from alkaline pulp waste liquid
JP2697054B2 * 1988-12-23 1998-01-14 住友化学工業株式会社 Method for producing p-hydroxybenzaldehyde
DE19532317A1 1995-09-01 1997-03-06 Haarmann & Reimer Gmbh Process for the production of vanillin and suitable microorganisms
CA2238215A1 * 1997-06-19 1998-12-19 Markus Wetli Process for the production of vanillin
CN1084724C * 1998-10-07 2002-05-15 亓平言 Vanillin extracting and purifying technology
FR2933974B1 2008-07-18 2010-09-17 Rhodia Operations PROCESS FOR SEPARATING AROMATIC ALDEHYDE
 
DK3264916T3 2015-03-06 2019-08-12 Citrus Junos S A R L EXTRACTION AND CONCENTRATION OF FLAVORS
FR3062652B1 * 2017-02-08 2020-10-16 Rhodia Operations NATURAL VANILLIN PURIFICATION PROCESS
JP6879959B2 * 2018-02-09 2021-06-02 長谷川香料株式会社 How to make vanillin
FR3099477B1 2019-07-30 2023-01-13 Rhodia Operations Natural vanillin compositions
FR3099478B1 2019-07-30 2021-07-09 Rhodia Operations Process for treating a composition comprising natural vanillin
CN111548260A * 2020-06-02 2020-08-18 上海欣晨新技术有限公司 Separation method of 6-methyl vanillin and vanillin
FR3114813B1 2020-10-02 2023-11-17 Rhodia Operations FERULIC ACID PURIFICATION
US20230373896A1 2020-10-02 2023-11-23 Rhodia Operations Purification of ferulic acid
FR3120629B1 2021-03-15 2024-01-19 Rhodia Operations Process for purifying vanillin or a vanillin derivative obtained by a biotechnological process
FR3120627B1 2021-03-15 2024-01-19 Rhodia Operations Process for purifying vanillin or a vanillin derivative obtained by a biotechnological process
FR3120628A1 2021-03-15 2022-09-16 Rhodia Operations Process for the purification of vanillin or its derivatives obtained by a biotechnological process
FR3125818A1 2021-07-27  Rhodia Operations Process for extracting ferulic acid and/or its salts comprising a step a) in which a biomass is extruded in the presence of a base
FR3134582A1 2022-04-15 2023-10-20 Rhodia Operations Process for preparing a compound of formula (I) by fermentation
FR3134583A1 2022-04-15 2023-10-20 Rhodia Operations Continuous process of growth of a microorganism
CN115010687B * 2022-06-14 2024-06-25 万华化学集团股份有限公司 Demulsifier, preparation method thereof and extraction process of vanillin
FR2984314B1 2014-01-17 PROCESS FOR PURIFYING VANILLIN BY LIQUID-LIQUID EXTRACTION


US-10428356-B2 2013-11-04 Methods of making vanillin via the microbial fermentation of ferulic acid from eugenol using a plant dehydrogenase Bgn Tech Llc
US-5573941-A 1988-03-17 Callus formation vanilla planifolia University Of Delaware
JP-H0787987-A 1990-04-19 Preparation of vanillin by biological conversion of benzenoid precursor Pernod Ricard Sa, ペルノ・リカルド
US-5128253-A 1991-05-31 Bioconversion process for the production of vanillin Kraft General Foods, Inc.
JP-H05117125-A 1991-10-22 Growth retaining agent for lawn Dainichiseika Color & Chem Mfg Co Ltd, 大日精化工業株式会社
JP-H05227980-A 1992-02-21 Production of vanillin and its related compound by fermentation Takasago Internatl Corp, 高砂香料工業株式会社
WO-9413614-A1 1992-12-10 Production of vanillin Quest International B.V.
JP-H0759534-A 1993-08-26 Production of sweetening seasoning Kikkoman Corp, キッコーマン株式会社
JP-H07115957-A 1993-10-21 Method for improving quality of grain distilling malt liquor Kikkoman Corp, キッコーマン株式会社
US-5866380-A 1994-09-13 Methods for bioconversion of ferulic acid to vanillic acid or vanillin and for the bioconversion of vanillic acid to vanillin using filamentous fungi Institut National De La Recherche Agronomique-I.N.R.A.
JP-H0889230-A 1994-09-26 Production of sake Kikkoman Corp, キッコーマン株式会社
WO-9634971-A1 1995-05-05 Method for producing vanillin using the bioconversion of benzene precursors Orsan
JP-H09206068-A 1995-09-01 Production of vanillin and suitable microorganism therefor Haarmann & Reimer Gmbh, ハーマン・ウント・ライマー・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング
JP-H09238675-A 1996-03-07 Yeast for new brewing Sanwa Shiyurui Kk, 三和酒類株式会社
EP-0904396-B1 1996-03-23 Production of vanillin Plant Bioscience Limited
TW-429242-B 1996-07-22 Vanillin, ferulic derivatives compounds, and it's vasodilatory vanilloid type β1-adrenoceptior antagonist Chen Ying Jiun, Lin Dung He
DE-19649655-A1 1996-11-29 Synthetic enzymes for the production of coniferyl alcohol, coniferyl aldehyde, ferulic acid, vanillin and vanillic acid and their use Haarmann & Reimer Gmbh
KR-100493538-B1 1997-02-07 Ferulic acid decarboxylase 교와 핫꼬 고교 가부시끼가이샤
IL-124800-A 1997-06-19 Microbiological process for the production of vanillin and guaiacol from ferulic acid Givaudan Roure Int
MX-PA98004891-A 1997-06-19 Process for the production of vainill Givaudanroure (International) Sa
JP-2000125840-A 1998-10-29 Production of shochu Kikkoman Corp, キッコーマン株式会社
HU-P0104772-A2 1998-10-31 Construction of production strains for producing substituted phenols by specifically inactivating genes of the eugenol and ferulic acid catabolism Haarmann & Reimer Gmbh.
MX-PA01004338-A 1998-10-31 Construction of production strains for producing substituted phenols by specifically inactivating genes of the eugenol and ferulic acid catabolism Symrise Gmbh&Ampco Kg
GB-2347424-A 1999-02-24 Peparation of Vanillin Derivatives Zylepsis Ltd
WO-0144480-A2 1999-12-14 Enzymes and genes used for producing vanillin Haarmann & Reimer Gmbh
DE-10144308-A1 2001-09-10 Genetic modification of Amycolatopsis spp., used in producing vanillin, e.g. from ferulic acid, involves contacting culture with transforming and different DNA, magnesium and cesium chloride and polyethylene glycol Haarmann & Reimer Gmbh
US-8053010-B2 2001-12-04 Bran and bran containing products of improved flavor and methods of preparation General Mills, Inc.
CN-1421523-A 2002-07-22 Aspergillus niger and its microbial conversion process of producing vanillic acid and vanillic aldehyde 江南大学, 浙江鑫富生化股份有限公司
US-2006172402-A1 2002-10-23 Production of vanillin in microbial cells Havkin-Krenkel Daphna J, Gerben Zylstra, Chaim Frenkel, Faith Belanger
JP-2009173670-A 2002-10-30 Method for producing plant processed product Suntory Holdings Ltd, サントリーホールディングス株式会社
JP-2004267131-A 2003-03-10 Method for producing vanillin by using alkalophilic bacterium Tsuno Rice Fine Chemicals Co Ltd, 築野ライスファインケミカルズ株式会社
US-2011268858-A1 2003-03-28 Preparation of vanillin from microbial transformation media by extraction by means supercritical fluids or gases Saf-Isis
CN-1544409-A 2003-08-19 Ferulic acid and ferulate preparation method 丽珠集团利民制药厂
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Process for the preparation of m-methoxy-p-nitrobenzaldehyde and ferulic acid for the production of vanillin M. ULRICH in Genf, Rue de Mole 1