PH26511A - A new microorganism for breaking sown moenomycins a process for the breakdown and the use of the breakdown - Google Patents

A new microorganism for breaking sown moenomycins a process for the breakdown and the use of the breakdown Download PDF

Info

Publication number
PH26511A
PH26511A PH39114A PH39114A PH26511A PH 26511 A PH26511 A PH 26511A PH 39114 A PH39114 A PH 39114A PH 39114 A PH39114 A PH 39114A PH 26511 A PH26511 A PH 26511A
Authority
PH
Philippines
Prior art keywords
breakdown
err
bad original
eee
tre
Prior art date
Application number
PH39114A
Inventor
Werner Aretz
Alois Tumulka
Dirk Bottger
Gerhard Seibert
Peter Weizel
Kurt Hobert
Original Assignee
Hoechst Ag
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hoechst Ag filed Critical Hoechst Ag
Publication of PH26511A publication Critical patent/PH26511A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/12—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/125—Saturated compounds having only one carboxyl group and containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/60—Unsaturated compounds containing ether groups, groups, groups, or groups the non-carboxylic part of the ether being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/26—Preparation of nitrogen-containing carbohydrates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/44—Preparation of O-glycosides, e.g. glucosides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
    • C12P7/42—Hydroxy-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/07—Bacillus

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Saccharide Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

It is possible with the aid of a Bacillus species or the appropriate enzymes obtained therefrom to degrade phosphoglycolipid antibiotics. The degradation products of the moenomycins have antibiotic activity or can be used as building block in the synthetic preparation of transglycosylase inhibitors.

Description

ft, 251i:
DESCRIPTION
Cv per aie cy annie me fone tir eal ing doen
L mone ines, a proces: Tor the breakdown, arn
Uh ne oo oof Fhe bp ooalaclbeomn yo acloee bes tlorestiomey re 11 iN (ria, ty i the main
Poona or f FY aveoynye ip why irs eed in liver tow! natriticn., {ike mhher brown phicorphoatealipid antibiotics it inhibits the hic unthe sic of the peptidoaglvean frameword of tle bar bey bind cell wall cln=esyr investigation chewed Phat Lhe bransaolvepay lation reacion of . thee pend C1 En binding preoein Th of E. coli is inhibited hes hea anhstances | Huber G.. fmbibintice, od pages 13% boo 193 (1979) 0.
Attempts alt =pecific ensymatic or microbial bec bdewn of phosphoglyeolipid antibiotics
Braves ib thes Foy fad led, .
Suey deine ly, a one Facil oe spec ies . - which ie ahle to oleace the phosphoglycaiipid 2A antihicotice to defined end products has now
Faeries fanlated from a contaminated fermenter
BAS BAD ORIGINAL font ther prepay al don ivf flavamyoin resin
Slr eplomeres ghanaenesis. these ed products have antibiotics artivity or can he geod aes boi Telling IV eve toa in Fhe mypy thy ie of Frese © rare by ote Taam duh bed Bove en
Hiesive ev dpvveennb ion relates tox 1. Bacillus ape, DSH ALTE and thee variants ard mutants they eof. oe, the cleavage proadact of moenomycin A 121th
The formed To ve ud LT . . . » ‘ 1A i
Wf . / / “ / re yy ne
Wwe 7. / J i PA pe ped _ | | . . py ’ H / -f ! / { re oo] we / I Jom ]
DE eee I. / , .
Ww | HA
Vy } ! . No ty 3 ; - ' ' bei
BAD ORIGIN
_.. ORIGINAL
{ (7A. 265 a. I hes Leanne py odue b of the phosphoaglveoliptd antibiotics with the general formula CL
A : . LO
FO He re
COOH arf 11 in which IY), is hydrogen or a phosphono ar oop [FO ST and Fig ds a (Cg to Ugg) -alkyl group which can be branched or ontgancehd. saturated or unsaloar ated, 1a the ED MES with those aid thes ’ phosphoglycolipid antibiotics can be cleaved at the phosphoolyoosidic linkage, or the ! cleavage pwwoducts speci fied under 5. can he . cleaved at the ponophosphate ester linkage. , a. AN process for the preparation of the
J breakdown prodie te specified under 2. and Il, : which comprises incubating phosphoglycolipld antibintice with Hacillus spec. DEM A675. »
LH. The usm of the substances specified under na 2. and 3. as building black for the synthetic
Cn BAD ORIGINAL ratiedtRG) OL . te tr—— .
Taf-2451
LY preparation of tranenlycoleylaae inhibitors or as subasbance having ant ihiotic activity.
The invention wilt be described in detail hereinafter especial ly in the prefer od bi) embed 3 men bes Tt de frag thermore defined in the cboavimes. Vo
Har illus ape. was deposi led with the rembeat DEM 4675 under the provisions of the
Hud appeal fy esaty al Lhe Deatache Sammlung von
Milt oorasaniesmen und Zelllbalturen GmbH ( German
Microorganism and Cell Coltuare Collection ) in
Br oannschuein, FRA, nan dune PF, 19889. Thea char acrtevistica of the alhiain may he aald to ! ber the fol Towing: 1. Tasonomic properties of Racillus ap. DSM
ALTH
0) Mor pho tony , ’ —- pottle rods: up to fom Jonas some in ’ shor tb chains . i lr — terminal spores sporangium swollen ‘ wo FBrameposibive. :
RY) Grevabh on various media (28"C: 48 hours) 1. Mntibiatic medium XT (Nofoo) . CLF . BAD ORIGINAL
-— — fel 7657
Co roh, tebed calonies af diameter 100 mm wn. Luria baoth (Batee Frwptone 10 g/l Racto weant Bogs lr Mall afl oo wrt by, ry leeey pond colonies of a chinese 207 mg opaque ~. fate ie broth (Di feo) : whi be, alossy colonies with dvr mul ary mar qin 4, Chr is tensern urea agar (Di foo) in : reve bh pes bse i. Me Conbey agar (Difoo)d — rowth positive 1 6. KEAN AC acar (tactose) (Difoo) caprene thy posi bie . 7. Qigmene citrate agar (Difoo) — growth negative .
Qa. Mor arawth in the presence of 7 or 160%
Hal'l in a peplone?meat exiract medium (Difoo) i fare oo .
To BAD ORIGINAL - - —————
fal. o6S H
CC) Fhysiological properties 1. Ouidase + wD. Catalase +
RIN Feemer ) yes doen - 0 1. Pminopopticdace -
Th. Flitrale pescdoe tion —-
AH. Phenylalanine deaminase - 7. Grewal hy at 3" 4p" 1 19 50" ‘- £1. finaervohic growth comedic -
Tiguir - @. fae formation from alucose - 1% 12. Indole formation - 10. Mr aindine dibydrase - ! trea hreakdown - 13. Facil in hydrolysis ’ + 11. Gieal at ine brealdouwn - 15, He Galactosidase + 14. Lysine dycarhouylase * - 17. Mrmithine decarboryl ase —-
Lt. HLS production : 1. fvyptophan deaminase -
BAD ORIGINAL fad. »és/ 20. Nval, phosphatase - »i. Voges Ty ok sauer peat don -
D) Fermentation of carbohydrates
Acid (0 cunt ven {yaa bmi tat ion formation
T futipictes
Alon i End fy shrines 1 +
Copy abe
Citrate .
Dieter terd -
Fructose + +
Gata Liver
Gluconate +
Glucose ¥ + th Foyer 3 Land lac tine ' +
Malate .
Matonale
Plead bose 1 +
Hannito) K +
IR EIRTATRLETE 4 +
Merl ibinse + 4
Frhearrsy Lace tale }
BE
Sal BAD ORIGINAL demented,
At, 65°17 ; Acid ot CC souree Nesziml bal von formation
Faffinnse 1 +
Fhamnnse oN IRINTN To 1 +
Galicin -
Sorbitol -
Trehalose + 4
Xylitol - - 19 Xp Yovse + +
Meaty ly alucosamine +
Taking account of tasonomic features and with the aid of "Rergey’ « Manual of
Qyaltematichacteriology" (Vol. 2,Williams and 1% Wilkins publ, , Raltimore, 1984) the strain can
I byes Aansigned to the genus Racillus, To determine the species, paral lel comparative estaminations of type cultures of Bacillus macerans, ociroculans, lentus, alcalophilus, » stearothermophil Tues, licheniformis, polymyxa antl fastidiosus were carried out, All the compar ison strains showed distinct differences
ORIGINAL
~ saDORGN a fait 265 . from Mach Llu: spac. DAI A678. Fn mere any of thee ahr aine ahle to bir enh downy phosphog le Mmlipid ant ihint irs, eaperially mooenomy cin 0. The come lusion to he dias a from This ia that strain DAM ALTH da a new
Spe Een,
The anvention alzmo relates in ead h case ter Lhe mutaats and variants vihich, as is
Foon, nay ar tee spontanoonc 1v ar he generated by treatment with physical agents, for enample irradiation, such as ultraviolet or Yop ays. OF wilh chemical motagens susch as, for example, erty] mest hanes) fona be (ESM), Homethyl-N pitro fen itrosomuantdine (MNMGY or 2-hydrony: 4 me thoy henzophenone (HOR).
Guitabhle and preferred as carbon source fen: the serohic fermentation of Bac illus spec.
DSH ALY are aszimi table oa v holiydr ates and shar ateotule, mueh ae 4g lucose, lactose or =a mannitol, as well as carbohydrate containing » paturad products such as malt extract. suilable and prefered nitrogen-containing fbr dents are: amine acids, peptides and 1a
NT fio .
Bh BAD ORIGINAL ———
Taf. 7¢ & 14 f1meste iy fermen tere, wher Appropriate
Introdur Jom adr ar aenvoern, The ferrmental inn oan [I place in oo bemper ature I (1 om appr ocimate ly room Fomper ature to 00) r, " proeforabhly ab ahouk m5 ba 570, The culturing
Vier is generally 24 bor 480 hearers hes cultures of Bacillos DSM ALT ahtained in this way, or preparations thereof,
IA ber ved Lo cleave 1 byes phosphog lyenl dpi 1 antibiol ices, There toe Lucker, in particular ther antibiotics of the onenomyoin group, for erample pholipomycin'’, the prasinomyc ins”), the diwnveins (macarbhomycins) 2 msanchomycin,
Fr errany rin and bed ehomy co dn, and od hes struct ally related aubstances which have a correspondingly functionalized phosphoglyceric ac td
I tH 4. Talkahashi et al... Tetrahedron Lett 1985, 1477 =a ) Celr Weisenborn et al... Mature 213, 1092 (17267) - + SG. Takahashi et al., Antibiot. 26, 542 (12773) 71. - 12 -
GINAL pAD OR!
Jud. 25 Hb preter ine, aver rer | ae dbs breakdown procdoe ta thereof, =e hy Aas pepbono o tryptone, fin thermore meal extracts, milled ceeds, fon example af corn, heans, esovheans or the cotton i phon N ie il lat ton poorer i clones from Fhe production af alophol, meat meals or yeast go br oar ber re ves] l jae ADC RLU aalta and fed bya lees | Tlie ne br iend moalut Lon may additional ty contain, for example, chlorides, car honates, aul fates or phosphates of the alkali melbals or allbaline earth metals, JC, } Fine Arve MAN) ANEIRED ATE additional inorganic war) bes
Ther qreowth of the gic rooroganiam and t ten 1 format ion of Phe ey yams yee ese mg oy for he bir cabdonm reac tions aecordinng boo The Anvention ie particul:a by goed dn a nutrient medium containing conn ebtarch, soybean meal, suet ose, glyraral, peplono and/or corn Steep as carbon oh and nd Leoaen soar ceo,
In Tet mentation ie carried onl amr oabhical by, that ia boy aay, for example, ebm oped with whaling or ebtiveing in ehh en 4
BAD ORIGINAL
SITY bo mm
. § } Vhee enzymes aro pay laicalarly preferably vaesese) to bp end: (hen the moenomyc ins, fea example for Flavomyein.,
I tyesny Hacillus aed are used it ia a abvan tage ons toy permeabilize The latter, fon emp be with cebtyiteimethy ammonium salts.
Ti: ie Pibewisr posesible to use protein taanlatbes from Bacillus cells, or NEY mes pula ls uhich have been partially enriched, 12 for example, by salting ont or chr omastoaraphy or, of course, the purified enzyme. It is furthermore possible to employ the enzyme and calle in free or immobilized form.
Thee enzymatic breakdown is depicted in . to the following diagram using moenomycin A As example, » -13-
BAD ORIGINAL er i » -
Enzymatic breakdown of moenomycin A ) - "Ne oon : } Hoo sory ’ Ho A . .
MO HO 0° . . re * Ae wef hae 0 . "
Moenomycin A
AR
° ve RD 00M - . Ho H “Psy
LL en .
H “ . . ' . ° RT “" - ° HAe ’ tom
Cs 0 " Mbase . MC wf Prose I~ . nok" . i
MA
EY
SAMI o }
Fad. 2051 a 7 —
Tr ds evident from this diagram thal bry eneyvmes are peoded ta py epare the cleavage produc tse An ens eme, which the inventors have called moonomycinases, io rogue ed to cleave bl the phosphaglyvonsidic Linkage, HMeenomy eo inase
Pe ascocialod with the cybtoplacmic mesnbr ane of
Fiori] Ls YEE NSE A520 and ean her obtained fromm the microorganism by ensyme isolalb ion methods boaoony per ao,
La Flexestaovmy eo dy ines es has a pl opt imun of abi d gon 03.5, inn particalar A,72 83.3. The temperature optimum of bho oneymes fs 45
S590, Hoenomyo dnase has a Kn, value Fear moenomycin A oof 4 1A mill iomalar .
Tier cleavage products are obtained. cleavage prodact 1 Compr iass the SLA
I
Component of the pho=phoglycolipid antibiotics, Alan obtained is the cleavane product with the gener al formals TR - ~ wo . . Apart
FOO CH OH FT
8}
COOH Ce. -15- 3INAL
- a
Jat 451! in which po! ie a phosphono aroun and rR isa
Ce bis Cope dma ll] aroup, prefer ahly a (Cim try
Cora Thy, in particular a (Con te Cog) alkyl " mach of which can he hranched or unbranched, ni calur ated (0 unsaturated, preferably tir anc hed and onsalue ated.
Mownomy ec ing are preferably employed Aas astrbyes Cra dienes, ae that the resulting cleavage produce Fe are the euhetaneces corresponding to the compoand PIC, as well aa the compounds MR . and HMO (see formula diagram). ne hey enzyme ia required for the depbosphor ylation of ob he phosphoglyeeric Ac id
Tiptd, which is ob Lianed by incubation with 1a movenomycinase, of the genera ) formula IIT in which Fry ia hydrogen, and can also he obtained ! fe om the microonrganiam according to the tnvenbinon. The Lnventors have called this enzyme Mhaae Mhase can likewise he isnlaterd from thee microorganism by methods known per . we. For ecample, the cells are dier upted with ultrasound, and the resulting crude ex tract is fre ther enriched either by ammonium 1 vl fate -16-
BAD ORIGINAL
——— ee
FAA
\ fuAf. 76S fractionation (29 - nn 7% saturation) on ultracentrifugation. This i followed hy dialysis. The moenomyeinase and Mhase are finally separated hy chy omatogr aphy .
I The Hhasme im increasingly inact ivated at temper ator os abese 7 ae well as when the pH falls in Fhe acid pi range be Lewy pl Si
This cleavage of the moenomyo ing, as well a= of the phosphoglyenlip id antibiotics can . iQ ae already mentioned, be cary ied out with : whole cells or enzyme isola Les. fhe reaction is generally carr ied out in Sov, aqueous medium a tr a pH of about 95.3 - B.5, preferably pH 7 of. The reaction time is generally OH 461 hour=, preferably abou tt 21 howe =. The reaction temperature oan be from 1 too AVC, preferably 20 te 27%, The substrate concentration ought to be dn the range from
Mm. to BY, pefer ally UL to 22%. ~ 29 1+ ism still possible to carry out the veac tion at temperatures or pH values whic h are higher oo Tease bhoan es bated, However , thes moenamas inane ig then leas ac bive.,
Ther reaction protacte vesal ting {1 em ’ meyerneny ec in 4} are {he aula ancea MR and He
A clesprio ed in the diagram. The proadact MIN can bier abvbatnesd by dnecubation of MB with MBase al
A ta 37, preferably alk 25 +n rte, and pH
G.7% Ha BN preferably pl A te 8, over a period of about 24 hoes, . 10 The =aid resction products can be used as antibiotic ( for etamp le MBY or as building bese |: for the synthesis of transalycosy lass inhibitors (for example FIN and MOY.
The tovention is descr ibed in more detail by mea aap) of examples, Unloae slated
I otherwise, pevcentane data relate tn weight.
Example 1 . »~
Maintenance of Lhe Facil ins spec. NSM 4677 atrain -18- BAD ORIGINAL rr ee —t
Ao a PERE . iy .
<
Jad 75 //
Hac illus eapec DSM 46 79 ig maintained on the following solid nate {ent medium (medium 1):
Bacto Lryptone (Difoo)d nn g/l 3 yeast outract (D1 feey) o/s fal 5 oarl fveyaat 15 g/1} nH FA fhe medinm 1s disbeibu ted over test tubes 1 ane ster ilezed at | ar M0 for TO minutes, then canled, inoculated with the ou ture and incubated at 279C for 2 oN years.
The arrow culture ja rinsed off to provide the inoculum for the following, maenomycin-containing ma in culture (medium 2): !
Carn starch ' 40 a/l
Goyhean meal a5 g/t
Sucrose 10 g/1 at, : 8 g/l jel ul Corn Steep 4 g/l
Cast, 20 mg/l -19-
BAD ORIGINAL
(oAt- 2451) @p Cally) polyglyocal cater 9S ml) “
HMoenomee in 0 Tas (ater ile filtered) pH 7.4
Th HAN ml Erdlenmyer flasks each containing owl oof this medium ave inocnlated and then incubated at THC snd toe pn for 03 : 143 bore a, final yeias of the culture filtrate hy thin Layee chr omatogr aphy shows that the 1 compounds Moy, MIE and ME are detectable as . Cleavage prodducte of moenomycin, and that
Coygay der Lhe ond oof Lhe fr eaction there has been
Complete disappeay ances of the MOTO YC aN eanprYoneend
Example 2 !
Freparation of cell-frrne extracts.
Ter propare call freo extracts, Bacillus
LB STATS DEM A675 dias cuttored in oa fermentor. .
For this, onllas are ringed of f the agar plate provide a 10 ml inoculum for a preculture -20~
B BAD ORIGINAL de Cea ot TTT
(500 ml of mediam 7 without BFlavomyodin io 0 ? 1 Fr ienmeyer flack) which fs then incubated at =rYC and 190 rpm far Pa hours. fno12 1 1aboratory fermenter containing 7 3 ] af medium To omediom 1s used far the main carl bore sbovgess
Fe bore 12.5% ag/1
Glyeer ol 0.9 tgs}
Citrate eB asl } read wo
Far t.% al
Mg s0 PRR HLL n.%n al
Freltl pr add, A. oll
Deamophen (propylene alyool) 5.0 mls ptt 6.8
This inoculated with S00 mw) of preculture and incubated at 37°C yy TAA ypm and an aeration rate of A. vvm for 24 hours,
The ron culture is centri fuaed, and the cell pazte is resuspended in potassium phosphate baffer (pH 7.0) 50 ot (1 9 of wet ces )es 2 ml oof buffer). her colls are they -21-
To BAD ORIGINAL disrnpted vith ultracsond, a French Press ot
Dyn Mitr, aned ther recall bing or ude extract is used for the conver sion,
Tri a test mixture containing 1000 wl of 0 crude extract, 192 mg at aoonomeae in and 200 al of potacsiim phosphate ha ffer (pH L.A) BA mH there te within 7-0 4 hours at m7, BT br ealbdown of the subsieate employed. The reaction products found are Hag MR and MC, ' 10 Example 3X
Freparative conpversion of moenomycin 0
Freparalive conversion are carried oat in a 12 1 fermenter containing A011 of potassium phosphate buffer (pHS.A HA mM, BOQ ml of crude !
Lh eneyme extract and 100 gq of moenomycin 0 at 2770 and 1M rpm. The progress of the
COMES 100) ie followed hy THE. the entire reac tb ionmicbuy ee ic froese-dried after 8 AR . . hours. The moenonyein breakdown is generally
A AR CY (WV analyeie from the TLC). the resulting reaction products are MOA, MB and MC. . BAD -2qe ORIGINAL fii MEL fof, 2657 /
Example 4
Frreparabion of the hreabdown produc bs 1A nn of freeze dried mixbore from the eneymatic conversion were taken up in 21 of -_ a wa les and eutracted bwice with © 3 of ert hyd acirbate earthy ime. Centrifugation wasneceaseary {oy complete phase copparation in thio Caeser, the combined organic ebrac tt were dried Cer sodium =o) fate, filtered and 1 evaporated toy dryness, n.4 g (0.4 7%) of a dart brown nil was obtained, and thin-layer chromatogr aply in the syste n-butanel /acetic acid/water = W170 on silica gel (Marck 60
Frag aluminum TLE sheets), spraying with mol yhdatophosphor ic acid/cerium(IV)sul fate color reagent (abbreviated to FMS reagen t hereinafter), showed that it comprised mainly component MO (Ff value = ABR).
The remaining agueous phase was then a evtracted twice with 2 1 of n-butanol each time. fine again, centrifugation Was perecsaty for phase separation. The combined -23-
BAD ORIGINAL
—— ee FE — 7)
Fut. PY tnt anal phason were then concentrated os ae possible, and the jesidus was taken up in a
Little water and finally jreere-dried, 7.4 qu (7.4 ¥) of a yellow powder were obtained and
J WET found on examination by thin--laye chr omatoar anhy (using the abovementioned conditions and Lhe came detection) to comprien mainly the component FBR = @, 52),
Fhe agueous phase from which non-polar subs lances had been romoved in this way was freeze ied, The amount of residue reaul bing from this waa 76.9 q (76.9 % with a total . y ’ amount of (5%), Thin layer chi omatography 1% ahowed that this pale yellow powder was composed of a polar main substance, called MO (RT = @.1), remaining moenomycin A and by- produc be, !
The orude products of Compe ts MA, MR 29 and MC obtained in this way were further pari fied aes follows, . -
PH
BAD ORIGINAL
——————————
SAVES f
Jad 2657)
Example 5
A) Furi fication of the hr oakdown prodoet 16 ney of Ma crude product wey es = chromatographed on 1020 q of silira gel (Mer cb
AQ, 15% 0 AR mem) which had heen adjusted to oa pH of SL, (The column matey ial hao heen prety erachend in the following way for thie
Ue see hey silica aed) was ativered Lo S50 ml 1 of SHY for one how 0 Ehen filteered off which suction and washed to nevtrality., the pi vas bheen adjusted to 70% with tH NaOH, and finally wvaahing with 21 of walter and S00 506 ml of methanol was carvied ont. the material pretreated in this way wag dried and activaterd at 120" overni abt). Chloroform/ethanol = 1/1 was vaed as eluent, the substance was loaded onto the column in J ml of orl vent mixture, and Pr6H fractions each of 2.5% ml were collected. Haing TLC analysis (TLC plates and » detection as in Frxample 1, solvent system as for column eluent), fractions 1159-179 were combined, dried on sodium sul fate amd finally -25-
BAD ORIGINAL
Jat o¢5 1 evapora bed tes drynige 27 mg of spectyroscapical ly pure MA were obtained.
Ir Ffarification of the breatdown product
MHA
NC ZZ. 1 a of Hit-cemtaining product from the extraction were chromatographed of 900 go of silica uel which had heen adjusted to a pH of 7.0 using the process explained in Frample 2.
Using ao medium pressure chr oomatooraphy aystem : 1a (MELE), chloraform/ethanal Zwater = 4/7/1.% was : weed for the elution at a flow rate of 310 ml/min and a pressure of 2 9 bar, After a fare-run of 00 ml, 220 fractions each of 10 ml wore cal lected, combining on the basis of 1% thee MO. Resides mised fractions containing
ME. fractions ?@ - 170 yielded 1.78 g of pure
ME after puvaporation, taking up in water and freese drying. ec) Fuarification of the breakdown product a
MC
2.00 a of polar crude product from the ~-26- — or BAD ORIGINAL —_ es
Gt 2087) aguurcars ployee of the cortbpact ion wer e Tilremi me chromatographed ander preogsare (HPLC). BAN of =ilicoh gel with a pl of 7.5 were employed (pr een in Frample DY, and fhe eluent vee] 1& Vines ehh l acetate propanal Swat om AABN
Phe amend for hex VTovaded wares suspended in methanol with 15% og nf silica gel, the elegy pas evapen Aber off, and the support treated in this way inbrodoaced into a precolamn, and then 16 er bo bd ow vias carried out al oa flow rate of 5 md Simin wander a ppeseare of Do A bar, No fore run af 990 ml owas followed by fractionation in fractions each of 10 ml, The fractions were tested by thine ayer chromatography in 19 the ayelom shity) acobate/i-propanal /water a 1/73/71 using FHS colar agent and detection oy f the NY absorption at THA my, and were ’ combined, Fiesea i eles: mi sted fractions, ’ . concentration of fractions 1220 190 to the 2) aqueous phase and subsequent freeze-drying pera lescd tt. 0 or f re Pe, which WA } investigated by spectroscopy. a “27m,
BAD ORIGINAL
Ce ———
24 2657)
Example 6&6
Elucidation of the structures of the products HA and MB obtained from mosnomycin A by ensymatic hreabtdown. ! “i he numbers of the structure relate to the formula diagram on page )
The structure deduced for MA was la. The assignment of the structure is on the 130 NMR pee trum of la. Fraction of 1a with 1 diaromalthane vielded the methel ester 1b which ie characterized by a by MME and an EI mass specioum,
The structure deduced for MB on. the basis of Me amd FAR mass spectrum was 2.
Hydrogenation of 2 yielded then decahydro derivative 3a which reacted with tiazomethane to give 3b, which had already been obtained previously from moenomy ce inh NAN by another ronates, Tt die consistentawith the proposed atructure that it was possible to convert 2 (MB) ensyinatically into ta (MR). -28- BAD ORIGINAL —_— ——
SA .
vo
Jat: 26571
Denese ar ipt beg eof Lhe enipey iments ia: 173. - -
CC OMMR (ta A HH, £DLODY 2 nevearnoe Lom moiety: foo AHF. (0 ty 12TH 0 TY, 143.4 and © 141. Qq(r and oF, RS and AR L0H (2-0 arn
C8), tan? (C6). TH.%9 (C-0), a." (C7),
SALT (6 fy, ART. (Cot), RRA (12). 122.7 (C13). P57. (0-14), Th. (Corsy, 27,7 (Lu
TAY, 125.0 (0-17), 132.2 (CR), PRL C19). 17.8 (C-20), 16.1 (C-21), 109.7 (C22) 27.7% (C--32 and C-24Yy, 27.08 (0-20), Glyceric acid moiety: Ro = 178%,9(0-1), 8.46 (L327, Ha.) (3,
Coghlan (A126. 6) ib: i ta was converted into the Ht form In agqueons solution using GI “A nt form ). 1a (H' form. 18.5 ma, 2.04 mmol) was dissolved in methannl (% ml) ant at ne, ONCeTY ethereal diazomethane solution wae added. The» ped reaction mixture was maintained at 29C for 2 h and at 20°00 fer 12 boand then evaporated to 29
BAD ORIGINAL
~~ -— — !
Vid 2657! dryness. Column chromatography (3 aq of Billy petroleum ether ethel acetate P21) yielded 1b (7% ma). ’
YWoomR (BAMHz, RCV): & = B.F6 (8, 6H,
CH 2% and Cis FAY, 1.41 (mn, 6H), 1.68 (s,
THY. LTE (=, THY (ACH), 1.900 - 2.12 (allyl
Hel, 2.4672 (broad do, J = 2Hz, ‘oh va 12). ZX.78R (eo (VCH 7) LOA ATA (OCH, and NCH signals),
A.A (broad =, CHL 27), 4.87 - 5.47 (olefinic
Hey C Unglignlly (2460.7), MS: o/= (%) = 460 (sy, PTA (1m, 20a (19), 1799 (68), AN (120), 25 Ce 1s Pi amr (pm. e Mhz, P20 yr moenoc ined ‘ moimty: & = 6.46 (0-1), 124.9% (C2), 142.9 (O-
TY, Lb (C44), BALA (0-5, C10), 128.1 (0-6),
IAT 6 (2-7), 37.8 (C-f), 44,1 (C9) ,1531.4 (0
LU), 37. 02 (0-1), 127. BO(0C-13y, 1738.3 (£14), 42.2 (0-18), 29.1 (C14), LELH.? (0-17), 133.1 (C16, 28.0 (C19), 192.9 (C20), 18.2 (C- 21). L112 (2-22), 29.7 (CRT, 24), 23.9 (C- 28). Glyceric acid moiety: & = 1792.0 (C-1, ~30=
BAD ORIGINAL
Wa ‘ -_—
tot, 2657/
AL. (02), GRA (0 AY Ub, DSF (B26, 7),
FOf-MS (matrices DHKO/alyveeral): msde = 619 (1
TAMA T, RET (MPH Ma) Dp 871 (M-HetHa
ARDY, PAT, TL, IRD LAB, 1A, 11h, i Jaz 2 (14.9 mag, 28.757 pmol) and Ft. (4 mq) were stirred in methanol (7% ml) and acetic acid (50 ul) in an Ho atmddhhere wider hormal ” TTT conditions for TF day=. the catalys was filtered off, and evaporation vielded Ja (13.9% nog). © Cage 05F (536.7), FAR-MS matrix: + 1 = pMEN/ Glyeerol: m/z = 625 (MeTHEANa) ss SEL (0
HE2MNa) 058 (M-HinayT, hai, Sha, 498, 475%, 404, TAZ, Ta0, P98, 288, M66, 1B6, 164, 142, 115, 95%, f 3b:
Jamas treated in aqueous solution with wr eve bs ety + i. the ion exchanger (Dowes: SB, HS form) dn order to liberate all acidic groups. The resin was filtered off and then the solution was freeze- dried, 2.5% mg (19.9 umol) of the sample -3t-
BAD ORIGINAL
Tat. 2S l/ treabed in Fhis way vere dissolved in methanal (0? mi). On pueess of eo ther eral diazomethane solution was added at °c. . The midttwe o .
Wis left ter skand abt AC for 2h and at hil 2000 for 13 hi, Fvaporation and column chy ama boar aphey (Hg of Si Ne . petroleum eller /ethyl acetate trl) vielded 2h (4.0 mg). i MEF (8 20 MHe, CDE) 3): om 7H (a,
CH and 2 Jd, 2d = 1A and 12 Hz, P{OCHy 9),
H,P
TLR 14.490 (LOCH 2 and OCH multiplets), . Coon NF (878.8), MS: n/z (%) = 856% (A.1.M- 13 63 7
CH, DR (1. M-CO0CH ) 452 (1, MM (CHO ) FOMOH), 581 (3, 1-0), Hog, breakage of the Tink hetween C82 and C9 of the 24% per hydromoenacinnl moiety), 229 (8, a) 217 (Ay bY), 127 (26), 97 (109), !
BAD ORIGINAL
— See
- ye Mo A . woo enzyme % Zz ~ <V XN
Hoenomycin A RO “0 1 |R a|H p : b |cH, enzyme : WooC ,, ~ z 2 a
NPGS ances ass
HO” xX 2 ~ H,/Pt
ROOC 0 ody . RO
RO” Np 3]r * aH 3 b| CHy
HCOOH H_ CH,0 PIOIOCH,);
MENA
—. HC —OH A
O=~C
Hy OPO} IOCH,) ! n HW” oc, Hig a b 4 . .
. fad. 2657
Example 7
Antibiotic activities of the oleavane proce ta
A agar dilution test with thael le-Hinton
MJ agar was carried eet to dotermine the antibacterial activities (Antibiotics in
Laboratory Medicine, VY. Lorian, Fd., Bal timore 1984, panes -1@Q).
Minimum inhibitory concentration (ug/ml) 19 Clmavage Str. Staph. E.coli products PvoQenes AUF eus 77 A pe2
Mn >in S100 S100 "ME 3100 28 >109
ME >100 S100 >100
Example 8
Tranasglycosylase assay -34-
Co Be BAD ORIGINAL
LS —————ad , :
s7/ :
Jat es 3474
The inhibition of the polymerization of the: peoptidoglye ans sugar chains he the olencaae prod bes wae caryied mat hey the Asnay decry bed hy bLeaki (0, Find, Chem 243%, TARE a) mA, 126RY u=ing lipid intermediates from the cell member ane of Fo oecodbid BOS,
It omerages from this that moenomycin nN (20 we sm) inhihits the transglycosylase reaction by B2.7 Y and the cleavage product MB 1a inhihite the enayme by 32.9%, ~ “35
AMES TAC gAD ORIGINAL

Claims (1)

  1. oT li i as ox Eihs B bd a ERR RLS TUARREIR fit cus er bgan RY KO gay FERRY © Trine Hi Tals Fp Ei Ca i BEC eh Pea HA aig ia» EEE RF hl dal no EON LET ST Bs lif A Sheen RR Fav 1b ast PR i” Fe LT af £3 i pe, EAP “heii A : . Sate Fit CL LEE of 00 Be ae vba Bh is
    > . i ade A Pas i Ln ERR SO bree len ~ 1 Cp er raat LC Se iid Wo hdr wv: el . Tang UR ASTRA daPekea Aid vr ue BT ei ff AE : DE Agel ! Sa CE 4 & /) rif) RNY Tetiysr i A Sia hE Gon Rel CE ir Ar AY. CAA Si *: paler 58 A eli J yo EA NE 7 TE = vet ; i) A> ~ Hd ; ir " Hh ie = Blab Se nA Td TEI . Ce SV AR TR Choe eb . ARIA Tl a or A SNR ro . oe . MRSA “ ERR Ee, Tae Ee J irr GR 1 ha ae Ge ON, wa ERLE 3 CSE ar 4 hy 4 a? J TL 1 IE RV. RA : Le PEN Hes 2.0 SE REY aman AA fF i RR hE 3 : bse ey Lan kA . HRT gf Ce un EL SR TA Ce aaa Gla ¥ « - . - - . '* yd . - . « A 4 . RR 3 SR te i apes Tg Chl HH HE ] 3 oy : Ce Co Ci . ET SEA py Co ] a nA . a } SER ee : Can 2 Le So SBE Co Cl ¢ ce it N on a Tk . Sad] : vo J “ I CE ims ign Se iv be - %i Patent Cla Lo : bo the Lo Co a | 5 ABH the Doo i . . . L “ ES 8 . a a #, So ' Aer ’ EEE so ot go “E DSM 467! RE Conky : Ts Sy 8 spec. : Agen eh wr % oa wh AH Bacillu [PE As i woe Ld Lm Fl “ : Cogn 1. of. Mg Ce To cf . oki mutants thereof: Ae fr dn 3 oo nL Lr d SE IRE ERAT Kr a Cems Eo cal Ea variants an Pe Cg al Co Geol Ae rv C Choo, wt spt Ch LR Co SEEK : SA SL Ey FET ng CLE robe wl ig F681 owing Ee 2 we Lyon fe = , ing - Lad J . ISR obs CR i Si cinase hav 1 wa : Le Bi : Je ne CARH 2 Moenomy og Pei ’ “ gtd 4 ie i OE . wl ‘ Bes r . ‘ R .. dp x . Sh Jen Fa rp Pei) 7 HER RE Tie Ep wy ORD iutics cid Co Fy . Re Wy . . he ah a . BR 2 . , a. } Boom Ug Eharacter GE xT CR Ce, = Xo , oooh 5, Lr SE eo = 4, . a 8 . SR gl : 3 of! ce at : “in a Roo be ANE Rah d antibintl Ti TE L MEE ai i YER lipid 8 ct ’ ) fee eo Bo “He tf phosphoglyco o CAR Long tRE HY | ge oO : TE CL Ce r ye sp et Lo . “TES cleavage - linkage oH ind ’ or ot ed on i bE 2 J : - Lt AE sidic hd Re We ot Cw . ll ; NS Co Ree hoglyco Si Coa A 2 AE? the phosp 8.8 LE Loh CBee Coden CEs to 8B. 3 : : Shana HANG pn ba Hg ® to 8.5 Ae | EI
    A. ve : Aa ee £ id timum of 8. ia sh SL ’ s ' Cau in i mn shes pH op = t an to Poon SI Cd AE ET optimum of 4 Cl di ion SE hei = ’ Lo Tre =r erature ' : Su is; Cy oa 4 {i : { kr HE . . on BE TRE a temp . . 10 ‘umolér + dat ne boo LL Snel ; HE Ca EEA ao Co TUM ! CoRR aE Fo y sel iT dy Ca 3 Ln . SL WREY > value of 4. ! ah PI. Se E A SE 3 Co TE KI . tA al a Loren ER so Ne a m substrate.” A : Lean See i Lh . a Ut . : ah ii, . Co TL La : Fn 10 a ucin A ams . . TOLIAREE . LE Td
    2k . “iD Ly moenomy ; i CRN SN veo ov RE Le
    ¥ . i } oa Bt 3 oo ¢ . ye RE il DSM ce va Fo : Le i WEE oi RAIA . Cat ash N14 CF te : i 3 Lt . Co . ’ . +, iE trom Baci 1 lus : . A . “ ol EN ne ga ; k : - THES zyme uta ChE nd af Co PE A Fee h . Ae ¥ An en Sy SA bo ES Fo a 4 3. : lates the 5 Lo Sr en sk SI . ’ so MEARS on Co : For on ge A 2 h dephosphory So SC : a Lo TL ck yo CE Ya678, whic EE ERE Pf To k: . . ay Celie . So Ch A Lo : CREE i ; Colne : ETE Ar LEE ON oy : - ph Ck he Formula ol Lh ; ny fo FT nL 1 - SE, - 5 eb Ln \ . Siw oo Lei EOUALREENES Pi LR TT Ee FREER: | Whe the ol Eh Eo ' ’ BD al. . “ : a ROS Cn fap Ha Loe oo ! re Lo BE Le. : ' 5 OF 1 wt 2 ) iH ary ro LH vd Sh CEE - A i” wr CE A oe -0R a ee Ca TL & 2 bs pe Ce 5 =o . gd Ru R. O-CH 2! - H OR, Loo oe ia bg: Le Cg ; : i £ } i SH . i . we EEE i . Co. RR 5 ; 2M CD OL Co i Bs fi ty RR Co. ABs aE — CTE CoA Eb ra AT ee wo i . vB “ jd : LN AL a a po fr? : < Rhu cL Ce RGAE, Ce sd ~ we ae i oR en haa SERN aphals: gro HB pes Lo 1 frei - A i RES we : i : or a pho ARE Loa ta © i A Lo “PR, ! ta hydrogen JARClirated Lal 3 oo K iy BN . Lr hy "a oy which R: So ted yoy AS Gen ra BN ig : } ¢ . gE 0. Or ; yy : TREY 3 r unbranc Cha 2 . CURE Rh Yo Abe Le Ly nched or | LL nd 4m HV oan x] iT - Is Es dR 2 is a bra Co Tey grot 3 = POE Co Ee py kK) I Rb Le 3 — To sl, FR x i © . gli } Sate an +3 c to Css )—a ; 2H a B CT FRU RS i rated (Cy to LoL Wd ERR fo Ric a unsatu Cr ae dda, gy +o woo CH ' \ AIS Ge te i; SP MEE : bea ¥ Si
    Lh . . RAR Poh . i Gat Sh - oy eed Ae oy : ¥? + Papen ro AR Coty cepa a [RA } io SE Jail ie 26 Cn hi hk Cn a | aly } Hy Fo Reed, shmm Go eel ih en Ly 1 Ss Co ‘BA BORG NAL SE -
    Lo . bi . : 4 Co AES co o 4 Cat WE Le TI a end ) Gp : Ce RR Cosel eT > aE . i Ao A ee h We so Fi Jaws ues i A Ca 5 : di Jie coy Co Le cheb NAT Lh Cra i Nate Yes, ToL WEES poiveniho bd N . ae Vl CRE Hy : Se TE 8 i Se ah hp CN Pi . i oo RAN Gok It. Rebar HH : oe Co ke Sk het oR Co SE ¥ Ce im, . eo 2: Fd | wt Ce aon Le oh ol Le L Ti : 3 ME Co “" bo a Sn So ore . GR lS Col Pa Tw, Wl " Cr a edt Ve en EL Hi : BY Perk CO i oe h oo
    Sh . ) ¥en ° Coo fat. 51) inactivated above 379C and when the pH ; decreases at pH below 9. . Werner Aretsz : Dirk @nttaer Gerhard Seibert . Alois Tumulle . (rater ble) rad roared Hebi Iaventors + i " . Co
    A ., ! 3g fy ~ . BAD ORIGINAL P \ A
PH39114A 1988-08-20 1989-08-18 A new microorganism for breaking sown moenomycins a process for the breakdown and the use of the breakdown PH26511A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE3828337 1988-08-20

Publications (1)

Publication Number Publication Date
PH26511A true PH26511A (en) 1992-08-07

Family

ID=6361268

Family Applications (1)

Application Number Title Priority Date Filing Date
PH39114A PH26511A (en) 1988-08-20 1989-08-18 A new microorganism for breaking sown moenomycins a process for the breakdown and the use of the breakdown

Country Status (16)

Country Link
EP (1) EP0355679B1 (en)
JP (2) JP2863557B2 (en)
KR (1) KR900003361A (en)
AT (1) ATE134641T1 (en)
AU (2) AU619034B2 (en)
DE (1) DE58909610D1 (en)
DK (1) DK407789A (en)
ES (1) ES2085855T3 (en)
FI (1) FI893878A (en)
GR (1) GR3019332T3 (en)
IL (1) IL91354A0 (en)
NO (1) NO893327L (en)
NZ (1) NZ230352A (en)
PH (1) PH26511A (en)
PT (1) PT91469B (en)
ZA (1) ZA896310B (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE134641T1 (en) * 1988-08-20 1996-03-15 Hoechst Ag NEW MICROORGANISM FOR THE DEGRADATION OF MOENOMYCINS, METHOD FOR DEGRADATION AND THE USE OF THE DEGRADATION PRODUCTS
DK0503419T3 (en) * 1991-03-08 1998-02-02 Hoechst Ag Method of Preparation of MA
US5316929A (en) * 1991-03-08 1994-05-31 Hoechst Aktiengesellschaft Process for the preparation of MA
EP0652205A3 (en) * 1993-11-04 1995-08-30 Hoechst Ag Moenomycin degradation products containing hydroxylated or oxidized lateral lipid chain and moenomycin analogs, process for preparing and their use.
DE19709897A1 (en) * 1997-03-11 1998-09-17 Hoechst Ag Bismuth salts of antibiotics of the moenomycin group, process for their preparation, their use and medicaments containing such salts
EP0872556A3 (en) * 1997-04-17 2000-06-14 Hoechst Aktiengesellschaft Process for the preparation of moenomycin A
EP1069130B1 (en) * 1999-07-15 2004-08-11 Hoechst Marion Roussel Moenomycin A Derivatives, their preparation, and use as antibacterial products

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL6601300A (en) * 1966-02-01 1967-08-02 Stamicarbon
EP0130327B1 (en) * 1983-05-21 1987-11-04 Hoechst Aktiengesellschaft Moenomycin-a derivatives, their preparation and their use as antibiotics
ATE134641T1 (en) * 1988-08-20 1996-03-15 Hoechst Ag NEW MICROORGANISM FOR THE DEGRADATION OF MOENOMYCINS, METHOD FOR DEGRADATION AND THE USE OF THE DEGRADATION PRODUCTS

Also Published As

Publication number Publication date
FI893878A (en) 1990-02-21
EP0355679A2 (en) 1990-02-28
JPH1171323A (en) 1999-03-16
KR900003361A (en) 1990-03-26
DK407789D0 (en) 1989-08-18
NZ230352A (en) 1991-07-26
IL91354A0 (en) 1990-03-19
PT91469B (en) 1995-05-04
EP0355679A3 (en) 1991-07-24
JP2863557B2 (en) 1999-03-03
NO893327D0 (en) 1989-08-18
DE58909610D1 (en) 1996-04-04
FI893878A0 (en) 1989-08-17
JPH02150273A (en) 1990-06-08
AU635452B2 (en) 1993-03-18
DK407789A (en) 1990-02-21
AU619034B2 (en) 1992-01-16
ATE134641T1 (en) 1996-03-15
NO893327L (en) 1990-02-21
ZA896310B (en) 1990-04-25
AU8835391A (en) 1992-02-06
GR3019332T3 (en) 1996-06-30
ES2085855T3 (en) 1996-06-16
EP0355679B1 (en) 1996-02-28
AU3998589A (en) 1990-02-22
PT91469A (en) 1990-03-08

Similar Documents

Publication Publication Date Title
Weiss Protoplast formation in Escherichia coli
Aragozzini et al. Indole-3-lactic acid as a tryptophan metabolite produced by Bifidobacterium spp
IWAMOTO et al. FR109615, a new antifungal antibiotic from Streptomyces setonii Taxonomy, fermentation, isolation, physico-chemical properties and biological activity
Archibald et al. The teichoic acids
EP0885957B1 (en) Process for the deacylation of cyclic lipopeptides
US4870165A (en) Antifungal antibiotics
PH26511A (en) A new microorganism for breaking sown moenomycins a process for the breakdown and the use of the breakdown
DK149336B (en) PROCEDURE FOR PREPARING ANTIBIOTIC A / 16686 OR ACID ADDITIONAL SALTS THEREOF
Biabani et al. δ-Indomycinone: a new member of pluramycin class of antibiotics isolated from marine Streptomyces sp.
HU188684B (en) Process for producing a2, and simultaneously produced a1 and a3 components of antibioticum a/16686
Joseph et al. Cellular localization of lipoteichoic acid in Streptococcus faecalis
Tsuchiya et al. Gualamycin, a novel acaricide produced by Streptomyces sp. NK11687 I. Taxonomy, production, isolation, and preliminary characterization
Isono et al. Studies on homomycin. II
Lesur et al. First access to a mycolic acid-based bioorthogonal reporter for the study of the mycomembrane and mycoloyltransferases in Corynebacteria
US5206405A (en) 2-alkenyloxy-3-(phosphono)oxypropanoic acids derived from the cleavage of phosphoglycolipid antibiotics
JP3097035B2 (en) Aryl sulfatase
US5260206A (en) Enzymes for breaking down moenomycins
US5506140A (en) Bacillus strain for breaking down moenomycins
Namiki et al. STUDIES ON THE α-GLUCOSIDE HYDROLASE INHIBITOR, ADIPOSIN II. TAXONOMIC STUDIES ON THE PRODUCING MICROORGANISM
US4517300A (en) Plasmid pSAN 181
EP0387712B1 (en) WS 7622 A,B,C and D substances, derivatives thereof, processes for preparation thereof and use thereof
KR970009151B1 (en) Ws-9326a, ws-9326b, and their derivatives
IE41640B1 (en) New antibiotic substances
YAGINUMA et al. Sporeamicin A, a new macrolide antibiotic I. Taxonomy, fermentation, isolation and characterization
Kuroda et al. FR-900137, A NEW ANTIBIOTIC I. TAXONOMY AND FERMENTATION OF THE ORGANISM, AND ISOLATION AND CHARACTERIZATION OF THE ANTIBIOTIC