β β β 1
!"#$%&'()* >?#,-% @AB 2;/0%,#FG% /0%, "-%,.% :9% #.-% 12-%,9%!"#$% +"# +"#% <=,#/0%,#DE% ".% 56% 34 78%!"#$% 2
β 3
4
!-Lactam Aminoglycoside 3 3 2 2 2 2 Penicillin G Kanamycin A 5
β 6
7
andidaasperugillus 8
9
23456Growth urve7 &'# / 0 % 1 $ %!"# $%# () # *+,+ -+. treptomyces 10
------cillin (Methicillin) ef------- (ephaloridine) treptmyces -----mycin Kanamycin Micromonospora -----micin Gentamicin 11
minimum inhibitory concentrationmi µ 12
β β 13
14
15
16
β 17
β ub MI + PAE post antibiotic sub MI effect (PAME) 18
19
6 p 197-255 β!!"#$%&'()*+,- 7 4 1 5 3 8 1 penam cephem monobactam penem cepham oxapenam oxacephem carbapenam carbacephem 20
Penicillin G 3 3 2 ( 2 ) 3 2 3 ephalosporin 2 ( 2 ) 3 3 2 2 ephamycin 21
β 22
3 3 Penicillin G Penicillin acylase 3 2 3 6-Aminopenicillanic acid (6-APA) Acylation 3 R 3 emi-synthetic Penicillin 23
!"#$%&'( 3 3 Methicillin 3 3 2 Ampicillin 3 3 arbenicillin 3 3 2 Talampicillin 3 3 β 24
β!"#$%&'()*+ 2 ( 2 ) 3 2 3 ephalosporin 2 3 2 7-Aminocephalosporanic acid (7-AA) 2 R 3 R 1 R 2 emi-synthetic ephalosporin 25
β 2 + e faloridine!"#$ 26
2 2 efotiam!"#$ 2 2 ( 3 ) 2 2 ( 3 ) 2 + eftazidime!"#$ 2 3 a + efsulodin!"#$ 2 3 3 Latamoxef!"#$%&'( 27
!"#$%&'()*+,-./012 3 7-methoxy R 1 R oxime A A R 1 R 2 7-AA 2 R 3 B 2 aminothiazole 3 -methyltetrazoylthio emi-synthetic ephalosporin ( 3 ) carboxyl (sufonic) A & B 345!6789:;<=>?@AB0,D E45F7G0I=>?@JIK,D L45MP=QQAB β β 28
!"#$%& 2 2 2 3 Thienamycin ( treptomyces cattleya ) 2 2 = 2 ( 2 ) 4 2 3 Imipenem ilastatin 3 3 2 2 Betamipron Panipenem!"#$%& ( 2 ) 2 2 ( 3 ) ulfazecin ( Pseudomonas ) 3 3 29
2 3 3 3 3 Aztreonam 2 2 3 2 2 arumonam!-!"#$%&'() 2 3 3 lavulanic acid ulbactam 2 2 Ampicillin 3 3 ultamicillin ulbactam 3 3 30
β treptomycesbacillusmicromonosporaaccharopolyspola 31
!"#$%&'()* 6 R 1 1 R 2 2 5 3 4 R 1 treptidine treptamine Deoxystreptamine R1 -=(2) -2-2 R2!"#$%&'()*+,-./01 6" 4" 5" 2" 1" 2 6 3" 3-D-Glucosamine 2 1 5 6-D-Glucosamine 2' 4' 3' 1' 6' 4 5' 2 2 2 3 Deoxystreptamine Kanamycin A 2 =( 2 ) 6 3 1 treptidine ( 2 )= 4 5 4' 3 1' 2' 5' 3' L-treptose 1" 5" 6" 3" 2" 4" 3 -Methyl-L-glucosamine treptomycin 32
33
!"#$%&'(Kanamycin A )*+ 2 3-D-Glucosamine 2 6-D-Glucosamine 2 P 3' 2 Deoxystreptamine 34
2 6-D-Glucosamine 2 2 2 3-D-Glucosamine Deoxystreptamine 4' P 2 2 2 3-D-Glucosamine 2 6-D-Glucosamine 6' 3 2 Deoxystreptamine 4" 2 3" 6" 5" 2" 1" 6 2 1 5 2 1' 4 2 3 2' 2 3' 5' 4' 6' 2 Dibekacin (DKB) 6" 4" 5" 2" 1" 2 6 3" 5 2 2 2 () 1 1' 4 2 3 2' 2 4' 3' 6' 5' 2 L-(-)-g-amino- a-hydroxybutyric acid Amikacin (BB-K8) 35
treptomyces!"#$%&'()*+,- 10 11 12 1 D B A 7 6 5 4 R 1 R 2 R 3 R 4 2 ( 3 ) 2 R1 R2 R3 R 4 xytetracycline Tetracycline Demethylchlortetracycline Doxycycline Minocycline 3 3 l 3 ( 3)2 36
!"#$%&'()*+, 22 + 8 x 2()2 -enzyme 2 3 2 2 R 1 R 2 R 3 R4 ( 3 ) Tetracyclines 37
14!" 3 9 12 3 3 5 ( 3 ) 2 3 3 3 1 3 3 Erythromycin 3 3 3 38
16!" 9 3 5 ( 3 ) 2 3 R 3 3 3 R 1 3 R 2 13 3 treptomyces, Micromonospora 1 Leucomycin!"#$%&'()*+(,- 2 3oA 4 x oa oa oa 3 9 5 3 R 1 3 13 1 39
40
treptomyces orientalis 2 3 3 2 vancosamine glucose l l 3 3 3 2 Vancomycin 41
(hloramphenicol) p 221 3 2 2 1 2 l 2 D-(-)- threo -1-p -nitrophenyl-2-dichloroacetamido-1,3-propanediol R 2 R 2 l 2 l 2!"#$%&'()*+ 1 2 2 3 1 2 L-erythro L-threo 2 D- erythro D- threo treptomyces venezuelae 42
!"#$%&'()*+,-./01234506 3 2 1 2 2 l 2 hloramphenicol hloramphenicol acetyltransferase 3 2 1 2 2 3 l 2 3 3 2 2 1 2 l 2 hloramphenicol acetyltransferase 3 2 2 1 3 2 l 2 3 43
treptomyces lincolnensis 3 2 2 3 3 3 3 2 2 3 3 l 3 Lincomycin lindamycin Bacteroides 44
treptomyces fradiae 3 P 2-3 P 3 Fosfomycin Phosphoenolpyruvic acid Rifampicinp 223 Rifamycin V Rifampicin "Ansa" aphthalenoid Benzonoid 45
3 3 3 3 3 3 3 3 3 3 Rifampicin 2 3-Formylrifamycin V 46
2 2 R 2!"#$%& ulfamine ulfoneamide p-aminobenzoic acid 2 3 2 2 3 2 3 3 ulfamethoxazole Trimethoprim 47
!"#$%&'$( 1 2 4 3 Pyridine!-pyridone "-pyridone )*+$ 8 1 6 4 Quinoline Quinolone 48
!"#$ 2 5 al idixic acid 3!%#$ 2 5 Pipemidic acid!&#$ 2 5 orfloxacin 6 F 49
!"#$%& 2 5 2 2 2 2 2 5 Ethambutol (EB) 2 2 p-aminosalicic acid (PA) Isoniazid (I) 50
p 233-234 3 19 2 3 Mycosamine 3 17 3 37 1 5 13 Amphotericin B 3 19 2 3 Mycosamine 3 17 3 37 1 5 13 ystatin 51
λmax360380405 nm treptomyces 52
!"#$%&'() l 2 2 l l l Miconazole 2 2 F F Fluconazole 53
D p 240-248 54
55
56
2 2 2 2 2 2 Aciclovir Vidarabine 2 2 3 Amantadine Rimantadine 3 2 n2 3 2 3 3!"#$% 3 zanamivir hydrate oseltamivir phosphate 57
Zidovudine Didanosine ( 3 ) 3 Indinavir 58
p 229 biological alkylating agents 5-FU 59
3 p 263 Actinomycin D p 263 DA deoxyguanosine intercalate RA polymerase ar = 2 2 X 2 2 Y L-Me-Val ar L-Me-Val ar 3 Z L-Pro D-Val L-Pro D-Val X Y Z Miitomycin A : 3 3 B: 3 3 : 2 3 L-Thr L-Thr 2 2 3 3 Actinomycin D 3 3 2 Doxorubicin Mitomycin p 264 treptomyces caespitosus ( 60
DA DA Anthracycline rubicin : Daunomycin Daunorubicin Adriamycin Doxorubicin Aclacinomycin A Aclarubicin Doxorubicin DA intercalate DA RA DA polymerace Daunomycin Adriamycin Aclacinomycin Adriamycin 4' 4'-epi-Adriamycin 1/2 Bleomycin p 264 treptomyces verticillus 61
DA DA DA BleomycinBleoA2 70% B2 30% PepleomycinPeplomycin : Peplo 2 2 2 3 2 3 3 3 R 2 Bleomycin A 2: R = 222( 3)2!"# $%&#'()*+,-./.0. 222( 3)Ph 2 2 eocarzinostatin Endiine 62
3 3 3 3 DA eocarzinostatin!"#$%&' p 275 p 275 iclosporin (cyclosporin A) T interleukin-2 TDM 63
TacrolimusFK-506 ciclosporin 100 3 3 3 3 3 3 3 3 3 3 3 3 iclosporin (yclosporin) Tacrolimus (FK-506) 64