JPS6078584A - Production of mycophenolic acid by fermentation method - Google Patents
Production of mycophenolic acid by fermentation methodInfo
- Publication number
- JPS6078584A JPS6078584A JP18804083A JP18804083A JPS6078584A JP S6078584 A JPS6078584 A JP S6078584A JP 18804083 A JP18804083 A JP 18804083A JP 18804083 A JP18804083 A JP 18804083A JP S6078584 A JPS6078584 A JP S6078584A
- Authority
- JP
- Japan
- Prior art keywords
- mycophenolic acid
- penicillium
- myo
- inositol
- growth
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 title claims abstract description 25
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 title claims abstract description 25
- 229960000951 mycophenolic acid Drugs 0.000 title claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 7
- 238000000855 fermentation Methods 0.000 title claims description 6
- 230000004151 fermentation Effects 0.000 title claims description 6
- 238000012258 culturing Methods 0.000 claims description 3
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 abstract description 19
- 229960000367 inositol Drugs 0.000 abstract description 19
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 abstract description 19
- 241000228143 Penicillium Species 0.000 abstract description 14
- 239000001963 growth medium Substances 0.000 abstract description 3
- 230000001737 promoting effect Effects 0.000 abstract description 3
- 201000004681 Psoriasis Diseases 0.000 abstract description 2
- 230000000843 anti-fungal effect Effects 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract description 2
- 230000000840 anti-viral effect Effects 0.000 abstract description 2
- 229940121375 antifungal agent Drugs 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 230000006698 induction Effects 0.000 abstract description 2
- 241000228145 Penicillium brevicompactum Species 0.000 abstract 2
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 238000012136 culture method Methods 0.000 abstract 1
- 229940098377 penicillium brevicompactum Drugs 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000002609 medium Substances 0.000 description 17
- 241000894006 Bacteria Species 0.000 description 6
- 239000000203 mixture Substances 0.000 description 3
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000013028 medium composition Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- FSRFQOAAESLDSG-UHFFFAOYSA-N 1-nitro-2-nitrosoguanidine Chemical compound [O-][N+](=O)NC(=N)NN=O FSRFQOAAESLDSG-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 1
- 241000549556 Nanos Species 0.000 description 1
- 241000864371 Penicillium viridicatum Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 239000006787 czapek-dox agar Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 229940014456 mycophenolate Drugs 0.000 description 1
- 230000037435 normal mutation Effects 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は発酵法によるミコフェノール酸の製造法に関す
る。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing mycophenolic acid by fermentation.
ミコフェノール酸は抗ウィルス作用、抗腫瘍作用、抗カ
ビあるいは抗菌作用を有する化合物であり、更には乾解
の治療にも有〃１であることが知られでいるＯＳミコフ
ェノール酸ペニシリウム属に属する微生物、例えば、ペ
ニシリウム・ゾレビコンノＪ？クタム（Ｐｅｎ ｉ ｃ
目１１ｕｍ ｂｒｅｖｆｃｏｍｐａｃｔｕｍ）、ベニシ
リウム・ストロニフェルム（Ｐ、ｓｔｏｌｏｎｊ４ｅｒ
ｍ）、ペニシリウム・スヵブルム（Ｐ、ｇｃａｂｒｕｍ
） ％ ペニシリウム・ナグミ（Ｐ、ｎａｇｅｍｉ）、
ペニシリウム・グリスコブルネウム（Ｐ、、ｇｒｉｓｃ
ｏｂｒｕｎｎｅｕｍ）、及びペニシリウム・ビリジカト
ウム（Ｐ、ｖｉｒｉｄｌｃｕｔａｍ）等によって生産さ
れることが知られている。Mycophenolic acid belongs to the OS Mycophenolate Penicillium genus, which is a compound that has antiviral, antitumor, antifungal, or antibacterial effects, and is also known to be effective in the treatment of psoriasis. Microorganisms, such as Penicillium zorebikonno J? Ctum (Pen ic)
11um brevfcompactum), Benicillium stoloniferum (P, stolonj4er)
m), Penicillium scabrum (P, gcabrum)
) % Penicillium nagemi (P, nagemi),
Penicillium griscobrunneum (P., grisc.
It is known that it is produced by P. obrunneum) and Penicillium viridicatum (P, viridlcutam).
本発明者等はよシミコツエノール酸生産能の高いミコフ
ェノール酸生産菌を育種することを目的として種々研究
を重ねた結果、ペニシリウム属に属するミコフェノール
酸生産菌にミオイノシトール役
によシ生育が遅進される変異株が著州のミコフェノール
酸を生成・蓄積することを発見し、本発明を完成するに
至った。The present inventors have conducted various studies with the aim of breeding mycophenolic acid-producing bacteria that have a high ability to produce cimicotenoic acid. As a result, the present inventors have found that mycophenolic acid-producing bacteria belonging to the genus Penicillium have been successfully developed to play the role of myo-inositol. They discovered that a mutant strain in which the production of mycophenolic acid is delayed produces and accumulates mycophenolic acid, leading to the completion of the present invention.
即ち、本発明はペニシリウム属に属しミオイノシトール
によシ生育が３進されるミコフェノール酸生産変異株を
培養して培養液中にミコフェノール酸を生成・蓄積せし
め、これを採取することを特徴とする発酵法によるミコ
フェノール酸の製造法に係るものである。That is, the present invention is characterized by culturing a mycophenolic acid-producing mutant strain that belongs to the genus Penicillium and whose growth is ternary due to myo-inositol, producing and accumulating mycophenolic acid in the culture solution, and collecting the mycophenolic acid. The present invention relates to a method for producing mycophenolic acid using a fermentation method.
本発明で使用する微生物はペニシリウム属に属Ａ免
しミオイノシトールによシ生育が炒進される性質を有し
ミコフェノール酸生産能を有する変異株でアシ、好適な
例としてペニシリウム・ブレビコンノやクタムＡＪ１１
７１１２ Ｆ障圓−Ｐ６６１９を挙けることができる。The microorganism used in the present invention belongs to the genus Penicillium, and is a mutant strain that has the property of promoting growth due to myo-inositol and has the ability to produce mycophenolic acid. AJ11
7112F-P6619 can be mentioned.
本発明においてミオイノシトールによシ生育が速進され
る性質とはミ茸イノシ） −／しを含有しない培地では
生育しないか又は生育が不充分であるが、ミオイノシト
ールを含有する培地で良好に生育する性質をいう。In the present invention, the property that myo-inositol accelerates the growth of mushrooms is that the mushrooms do not grow or grow insufficiently in a medium that does not contain them, but they grow well in a medium that contains myo-inositol. Refers to the property of growing.
本発明ではミオイノシトールによシ生育が速進される菌
株として、ミオイノシトールによシ生育が速進される性
質の他に他のアミノ酸、核酸等の要求性を付与した、更
にミコフェノール酸生産肯目の高い変異株を使用するこ
ともできる。In the present invention, as a strain whose growth is accelerated by myo-inositol, in addition to the property of accelerating growth by myo-inositol, the strain has requirements for other amino acids, nucleic acids, etc., and it also produces mycophenolic acid. It is also possible to use mutant strains that have a high profile.
本発明のミオイノシトールによシ生育が速進さレルミコ
フエノール酸生産菌は、ペニシリウムｉに類するミコフ
ェノール酸生産菌、例えばペニシリウム・プレビコンノ
ぐクタムＱＭ８４０６ＡＴＣＣＩ ６０２４．６るいは
ペニシリウム・ストロニフエルムＡＴＣＣ１０１１１等
を親株とし、これら親株の胞子に通常の変異誘導操作、
例えばＮ−メ５−ル−Ｎ′−二トローＮ−二トロソグア
ニジン、メチルメタンスルホネートの如き薬剤処理、あ
るいは９８外線照射を施して変異を誘起せしめ、レプリ
カ法にてミオイノシトールを含まない最少培地で生育し
ないか又は生育が不充分であるが、ミオイノシトール含
有最少培地で良好に生育する変異株を選択することによ
って採取される。The lermicophenolic acid-producing bacteria whose growth is accelerated by myo-inositol of the present invention are mycophenolic acid-producing bacteria similar to Penicillium i, such as Penicillium plebiconnoguctum QM8406 ATCCI 6024.6 or Penicillium stroniferum ATCC10111. are the parent strains, and the spores of these parent strains are subjected to normal mutation induction operations,
For example, mutations are induced by treatment with drugs such as N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanesulfonate, or by irradiation with 98 external radiation, and the replica method is applied to a minimal medium containing no myo-inositol. Mutant strains that do not grow or grow insufficiently in myo-inositol-containing minimal medium are selected.
本発明を実施する際に用いられる発酵用培地としては、
通常のミコフェノール酸生産に用いられる公知の培地、
例えばＷ、 Ｌ、 Ｍｕｔｈ ｅｔ ａｌ。The fermentation medium used in carrying out the present invention includes:
Known media used for normal mycophenolic acid production,
For example, W, L, Muth et al.
Ａｎｔ１ｍｉｃｒｏｂ＋ Ａｇｅｕｔｇ Ｃｈｅｍｏｔ
ｈｅｒ、＋ ８ ＋ ３２１〜３２７（１９７５）記載
の培地等が使用される。培養条件は従来法と同様に好気
的条件下に深部培養あるいは静置培養を行えば良く、温
度は２０〜３５℃、望ましくは２５〜２８℃の間がよい
。培養時間は１００〜５００時間、好ましくは１７０〜
４５０時間である。Ant1microb+ Ageutg Chemot
The culture medium described in Her, + 8 + 321-327 (1975) is used. The culture conditions may be deep culture or stationary culture under aerobic conditions as in the conventional method, and the temperature is preferably between 20 and 35°C, preferably between 25 and 28°C. The culture time is 100 to 500 hours, preferably 170 to 500 hours.
It is 450 hours.
かくして得られた培養液からミコフェノール酸を採取す
るには公知の方法が使用出来る。又培養液中のミコフェ
ノール酸の蓄積量は高速液体クロマトグラフィーによシ
簡単に分析定量される。Known methods can be used to collect mycophenolic acid from the culture fluid thus obtained. Furthermore, the amount of mycophenolic acid accumulated in the culture solution can be easily analyzed and quantified by high performance liquid chromatography.
以下実施例により、本発明を更に具体的に説明するがこ
れによシ、本発明が限定されるものではない。The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto.
実施例１
ペニシリウム・ブレビコンノぐクタムＡＪ １１７０９
６ＦＥＲＭ−Ｐ ５６９３をツアペック・ドックス氏寒
天培地で培養し、１０日間培養後胞子を集めて０．０５
％ラウリル硫酸ナトリウム溶液に懸濁液にＮ−メチル＝
Ｎ′−二トローＮ−ニトロソグアニジンを加え（濃度１
０００μｇ／ｍｌ ）室温に１０分間保持して変異処理
を行った。次いで胞子を洗浄し、第１表に示す組成の天
然培地グレートに接種し、２７℃にて５日間培養した。Example 1 Penicillium breviconnoguctum AJ 11709
6FERM-P 5693 was cultured on Czapek-Dox agar medium, and after 10 days of culture, spores were collected and 0.05
% N-methyl in suspension in sodium lauryl sulfate solution
Add N'-nitro N-nitrosoguanidine (concentration 1
000 μg/ml) was kept at room temperature for 10 minutes for mutation treatment. The spores were then washed, inoculated onto a natural medium grate having the composition shown in Table 1, and cultured at 27°C for 5 days.
第１表培地組成
グルコース １，０（イ） ３．０
ペゾトン ０．２−
麦芽エキス ０．１−
酵母エキス ０．１−
ＮａＮＯｓ −０，３
ＫＷ２ＰＯ４−０，１
ＭｇＳＯ４・７Ｈ２０−０，０５
ＫＣ１Ｏ，０５
ＦｅＳＯ４’７Ｈ２０−０，０１
塞 天 １．５１．５
このプレートを第１表に示す組成の最少培地プレート及
びミオイノシトールを０．０１％添カロした最少培地プ
レートにレプリカし、最少培地には生育しないか、又は
生育が不充分で、ミオイノシトール含有最少培地で良好
に生育するコロニーをミオイノシトール要求株として分
離した。このようにして分離したミオイノシトール要求
株の中にはミコフェノール酸生産能の高いものが多く見
い出された。その内代表的菌株としてＡＪ１１７１２２
ＦＥＲＭＰ−，７ユ９／及びＡ Ｊ １１７１２３ Ｆ
ＥＲＭｐ−７ユ７ユを選択した。Table 1 Medium composition Glucose 1,0(a) 3.0 Pezotone 0.2- Malt extract 0.1- Yeast extract 0.1- NaNOs -0,3 KW2PO4-0,1 MgSO4・7H20-0,05 KC1O ,05 FeSO4'7H20-0,01 Block 1.51.5 This plate was replicated to a minimal medium plate with the composition shown in Table 1 and a minimal medium plate supplemented with 0.01% myo-inositol. Colonies that did not grow or grew insufficiently and grew well on myo-inositol-containing minimal medium were isolated as myo-inositol auxotrophs. Among the myo-inositol-requiring strains isolated in this way, many were found to have high mycophenolic acid production ability. Among them, AJ117122 is a representative strain.
FERMP-, 7U9/and A J 117123 F
ERMp-7yu7yu was selected.
ＡＪ１１７１２２ ＡＪ１１７１２３を天然培地で２７
℃にて１０日間培養後、胞子を採取し、０．０５Ｍリン
酸緩衝液（ｐＨ６，８）て洗浄し第１表の最少培地及び
ｏ、ｏ１ｓミオイノシトール含有最少培地に接種１，２
７℃で７日間培養して生育度を調べた。その結果を第２
表に示す。AJ117122 AJ117123 in natural medium 27
After culturing at ℃ for 10 days, the spores were collected, washed with 0.05M phosphate buffer (pH 6, 8), and inoculated into the minimal medium shown in Table 1 and o, o1s myo-inositol-containing minimal medium 1 and 2.
The cells were cultured at 7°C for 7 days and the growth rate was examined. The result is the second
Shown in the table.
第２表に示す結果から、ＡＪ１１７１２２はミオイノシ
トール無添加最少培地では生育せず、ＡＪ１１７１２３
はミオイノシトール無添加プレート培地で生育が不充分
であることが１．（され、両菌株ともにミオイノシトー
ルによシ生育が速進される。From the results shown in Table 2, AJ117122 does not grow on myo-inositol-free minimal medium, and AJ117122 does not grow on myo-inositol-free minimal medium.
1. Growth is insufficient on plate medium without myo-inositol. (The growth of both strains is accelerated by myo-inositol.
第３表に示す組成の培地を３００ ｍｌ容三角フラスコ
に５０ｍＡ宛分注し、１２０℃で１０分間加熱、滅菌し
た。A culture medium having the composition shown in Table 3 was dispensed into a 300 ml Erlenmeyer flask at 50 mA, and sterilized by heating at 120° C. for 10 minutes.
この培地に試験菌を１白金耳完接種し、２７℃にて１０
日間２００ ｒｐｍで回転培養を行った。得られた培養
液中のミコフェノール酸含量を高速液体クロマトグラフ
ィーによシ測定し、生育は菌体を１０５℃、１６ｈｒ乾
燥し、その重量を以って示した。その結果を第４表に示
す。One platinum loop of test bacteria was completely inoculated into this medium, and the test bacteria was incubated at 27℃ for 10 minutes.
Rotational culture was performed at 200 rpm for days. The mycophenolic acid content in the obtained culture solution was measured by high performance liquid chromatography, and the growth was expressed by the weight of the bacterial cells dried at 105° C. for 16 hours. The results are shown in Table 4.
第３表培地組成（ｐＨ４，５）
グリシン １．４６ 〃
メチオニン ００５〃
ＫＨ２ＰＯ４０，３／／
ＭｇＳＯ４−７Ｈ２００，１＃
Ｆｅ１ｏ４２．Ｏｐｐｍ
ＣｕＳＯ４０，：３ ｔｔ
ＺｎＳＯ４０，２５ｐ
ＭｎＳＯ４０，１６Ｊ’
に２ＭｏＯ４０，０２ｔｔ
第４表に示す結果からミオイノシトールにより生育が速
進されるＡＪ１１７１２２およびＡＪ１１７１２３は親
株ＡＪ１１７０９６よりも高いミコフェノール酸蓄積を
示すことが確認された。Table 3 Medium composition (pH 4,5) Glycine 1.46 Methionine 005 KH2PO40,3// MgSO4-7H200,1# Fe1o42. Oppm CuSO40,:3 tt ZnSO40,25p MnSO40,16J' to 2MoO40,02tt From the results shown in Table 4, AJ117122 and AJ117123, whose growth is accelerated by myo-inositol, exhibit higher mycophenolic acid accumulation than the parent strain AJ117096. confirmed.
出願人味の累株式会社
手続補正Ｉ１
１、事件の表示
昭和５８年特Ｗ［願第 ｊＢＯ４０Ｍ
２、発明の名称
発酵法によるミコフェノール酸の製造法３、補正をＪる
者
事件との関係 特許出願人
住所 東京都中央区京橋−］１５番８号５、補正にＪ：
り増加づるブを明の数 なし６、補正の対象 明ｍ書の
発明の詳細な説明の欄７、補正の内容
明ＩＩＩ用第３頁、２行目のｒＡＪ１１７１１２ Ｆ［
ＥＲＭ−Ｐ４Ｏ１０を」をｒＡＪ１１７１２２ ＦＦＲ
Ｍ−Ｐ７２９１おにびΔＪ１１７１２３ ［ＥＲＭ−Ｐ
７２９２を−１に８１正りる。Applicant Ninami no Sumitomo Co., Ltd. Procedural Amendment I1 1, Indication of the case 1988 Patent W [Application No. jBO40M 2, Name of the invention Process for producing mycophenolic acid by fermentation method 3, Relationship with the case of the person making the amendment J Patent Applicant address: Kyobashi, Chuo-ku, Tokyo -] 15-8-5, J for amendment:
Number of lights to increase the number of blocks None 6, Subject of amendment Column 7 of detailed explanation of the invention in Book M, Contents of amendment rAJ117112 F[ on page 3, line 2 for Clarification III
ERM-P4O10” rAJ117122 FFR
M-P7291 Onibi ΔJ117123 [ERM-P
Correct 7292 by 81 to -1.
以上that's all
Claims (1)
れを採取する仁とを特徴とする発酵法によるミコフェノ
ール酸の製造法。A method for producing mycophenolic acid by a fermentation method characterized by culturing and accumulating mycophenolic acid in a culture solution, and collecting the kernels.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18804083A JPS6078584A (en) | 1983-10-07 | 1983-10-07 | Production of mycophenolic acid by fermentation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18804083A JPS6078584A (en) | 1983-10-07 | 1983-10-07 | Production of mycophenolic acid by fermentation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6078584A true JPS6078584A (en) | 1985-05-04 |
Family
ID=16216617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18804083A Pending JPS6078584A (en) | 1983-10-07 | 1983-10-07 | Production of mycophenolic acid by fermentation method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6078584A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006038218A1 (en) * | 2004-10-05 | 2006-04-13 | Biocon Limited | Process for producing mycophenolic acid using penicillium arenicola bicc7673 |
-
1983
- 1983-10-07 JP JP18804083A patent/JPS6078584A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006038218A1 (en) * | 2004-10-05 | 2006-04-13 | Biocon Limited | Process for producing mycophenolic acid using penicillium arenicola bicc7673 |
| US7625727B2 (en) | 2004-10-05 | 2009-12-01 | Biocon Limited | Process for producing mycophenolic acid using Penicillium arenicola BICC 7673 |
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