mikroba penghasil antibiotik - · pdf filemenghambat sintesis peptidoglikan. ætarget:...
TRANSCRIPT
![Page 1: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/1.jpg)
Mikroba Penghasil Antibiotik
Antibiotik metabolit sekunderhambat pertumbuhan org lain pd konsentrasi redah
Alexander Fleming (1929)Penicillium notatum hambat staphlococcus
Awal era antibiotikPerkembangan : - 1963 513 atb
- 1974 4076 atb- 1980-an 6000 atb
Produksi antibiotik FermentasiSemisintetik
![Page 2: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/2.jpg)
Mikroba penghasil antibiotik:
Bakteri, Actinomycetes, & Cendawan
Fungi :-Phycomycetes 14 atb-Ascomycetes 299 atb
-Aspergillacea 242 atbPenicillium 123 atbAspergillus 115 atb
-Basidiomycetes 140 atb-Fungi inperfecti 315 atb
-Moniliales 269
![Page 3: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/3.jpg)
Mikroba penghasil antibiotik:
Bakteri :
-Pseudomodales 87 atb-Pseudomodaceae 84
-Eubacteriales 274 atb-Enterobacterilaceae 36 atb-Micrococcaceae 16 atb-Lactobacillaceae 28 atb-Bacillacea 171 atb
Bacillus 167 atb
![Page 4: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/4.jpg)
Mikroba penghasil antibiotik:
Bakteri :
-Actinomycetales 2078 atb-Mycobacteriaceae 4 atb-Actinoplanaceae 18 atb-Streptomycetaceae 1950 atb
- Streptomyces 1922 atb-Micromonosporaceae 41 atb-Thermoactinomycetaceae 17 atb-Nocardiaceae 48
![Page 5: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/5.jpg)
Klasifikasi Antibiotik:
1. Atb mengadung karbohidrat- gula murni nojimisin- aminoglukosida streptomicin- Ortomisin Everninomisin- N-gliksida sterptotrisin- C-glukosida Vancomisin- glikolipid Moenomisin
2. Makrosiklik lakton- Atb makrolida erytromisin- atb polyene Candisidin- ansamisin Rifamisin- Makrotetrolida tertranamisin
![Page 6: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/6.jpg)
Klasifikasi Antibiotik:
3. Atb quinon- tetrasiklin tertrasiklin- anthrasiklin adriamisin- naftoquinon actinorhodin- benzoquinon mitomisin
4. Peptida & asam amino- turunan as. amino cycloserin- β-laktam penicillin- peptida basitrasin- chromopeptida actinomisin- peptida pengkelat bleomisin
![Page 7: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/7.jpg)
Klasifikasi Antibiotik:
5. Heterosilik + nitrogen- nukleosida polimiksinin
6. Heterosiklik + oksigen- polieter monensin
7. Turunan Alisiklik- turunan sikloalkana sikloheksimid- steroid asam fusidat
8. Aromatik - turunan benzen kloramphenikol- aromatik eter novobiosin
9. Atb alifatik- syw + fosfor fosfomisin
![Page 8: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/8.jpg)
Aplikasi antibiotik:Spektrum atb : - luas aktif untuk berbagai organisme
- sempit aktif pada orgamisne tertentu
1. Antitumor : syw sitostatik2. Penyakit tanaman :
awal: - streptomisin Xanthomonas oryzaePseudomonas
3. Pengawet makanan : aturan penggunanaanpiramisin : - permukaan makanan
- fungisidatylosin : - efektif thd spora bacillusnisin : efektif thd clostridia
Makanan kaleng
![Page 9: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/9.jpg)
Aplikasi antibiotik:
4. Makanan ternak : memicu pertumbuhan ternak
5. Studi biokimia & biologi molekuler : selective inhibitor: - penting utk pelajari fungsi sel
Germ freeAplikasi aturan !!!
-replikasi DNA- transkripsi-Translasi-Sintesis dinding sel
![Page 10: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/10.jpg)
Nilai ekonomi antibiotik:
Produksi lebih dari 100 000 ton per tahunTh 1980: penjualan + $ 4.2 milyarDi US + $ 1 milyar per tahun: 1. Cephelosporin
2. TetrasiklinUtk makanan ternak: + $ 100 juta per tahun
-sebelum 1960 : 5 % isolat baru atb digunakan utk terafeutik-Selanjutnya banyak isolat ditemukan-Atb yg di pasarkan %-nya turun : - 1961-1965 : 2.6 %
- 1966 –1977 : 1 %
Tingginya biaya produksi & uji klinis
![Page 11: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/11.jpg)
Jumlah besar syw atb yang diketahui
Pencarian atb baru masih dilakukan ???
Atb alami tidak optimal utk terafeutikperlu pengembangan:
- peningkatan aktivitas- mengurangi efek samping- memperluas spektrum-meningkatkan selektivitas
Adanya perkembangan resistensi
Modifikasi secara kimiawiModifikasi secara genetik: - mutasintesis
- DNA rekombinan- fusi protoplas
![Page 12: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/12.jpg)
Antibiotik β-Laktam
PenisilinCephalosporinCephamisin
Antibiotik peptida
Antibiotik efektif
Penilisin:-Fleming (1929) Penicillium notatum-Diisolasi th 1940-Pertama digunakan th 1941-Dihasilkan oleh banyak fungi: - Penicillium
- Aspergillus
![Page 13: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/13.jpg)
Penisilin alami: efektif thd banyak bakteri Gram positiflabil thd asamdiinkativasi oleh penisilin β-laktamase
Cincin Β-laktam
Menghambat sintesis peptidoglikantarget: transpeptidase & D-alanin karboksipeptidase
Polimerase peptidoglikan terhambat
Hambat sel yang sedang tumbuhTidak hambat sel yang tidak tumbuh
![Page 14: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/14.jpg)
Struktur dasar dari penisilin: 6- asam aminopenisilat (6-APA)
Terdiri dari cincin thiazolidin dg cincin β-laktam
6-APA membawa berbagai macam gugus akil
Fermentasi tanpa prekursor akil produksi bermacam penisilin alami
Hanya benzilpenisilin yg berguna utk terapeutik
+ prekursor akil produksi penisilin yg diinginkan
![Page 15: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/15.jpg)
Residu gugus akil 6-asam aminopenisilat
Cincin β-laktam
Cincin thiazolidin
Struktur Penilisin:
![Page 16: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/16.jpg)
Produksi komersil: - Alami Penisilin G,V, & O
-semisintetik: Penisilin G secara kimia or enzimatik
Split 6-APA
Dibuat turunannya + syw akil
Penisilin akilase
![Page 17: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/17.jpg)
Biosintesis:
Cincin β-laktam-thiazolidin ;dikontruksi dari L-cystein & L-valinproses non ribosomal: tripeptida 2 aa & L-α-asam aminoadipat
(L-α-AAA)
Produk I dari siklisasi : isopenisilin N(reaksi biokimianya belum dimengerti)
Benzilpenisilin: pertukaran L-α-AAA dg asam penilasetat teraktivasi
![Page 18: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/18.jpg)
HOOC-CH-CH2-CH2-CH2-COOHNH2
L-α-Asam Aminoadipat (L-α-AAA)
L-α-AAA-Cys
Cys
L-α-Aminoadippyl-Cysteinil-D-ValineVal
Siklisasi 2 tahap
Isopenilisin N
L-α-AAA– N S
NCOOH
O
H
Penisilin transakilase
fenilasetat
L-α-AAA-CoA-SH
Benzil-penisilin
-CH2-CO– N S
NCOOH
O
H
Biosintesis penisilin:Penicillium chrysogenum
![Page 19: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/19.jpg)
Biosintesis penisilin:dipengaruhi [fosfat]Direpresi glukosa
Fermentasi menggunakan laktosagula yg dimotabolisme lambat
Pengembangan galur:
Produksi : galur Fleming = 2 IU/mlsekarang = 85 000 IU/ml
Peningkatan dari 0.0012 g/l 50 g/l
Program Seleksi galur & mutagenesis
Dimulai th 1943
![Page 20: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/20.jpg)
Metode produksi:
Penisilin G & V diproduksi dg proses fermentasi submergedkapasitas 40 000– 200 000 literaerobik kendala suply O2 tdk bisa lebih besar
![Page 21: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/21.jpg)
Kurva pertumbuhan produksi penilisin :
produksi selama 40 jamDoubling time 6 jam:
-pembentukan biomassaDg fed-batch:
- spi 120 – 160 jam
![Page 22: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/22.jpg)
kembali
![Page 23: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/23.jpg)
kembali
![Page 24: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/24.jpg)
kembali
![Page 25: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/25.jpg)
kembali
![Page 26: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/26.jpg)
kembali
![Page 27: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/27.jpg)
kembali
![Page 28: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/28.jpg)
Cephalosporin Cincin β-laktam + dihidrothiazin
Cephalosporium acremonium : - isolasi atb th 1953- isolasi galur th 1945
Acremonium chrysogenum - Cephalosporin- Penisilin NCephalosporin steroid P1-P5
Cendawan : - Emericellopsis- Paecilomyces
Streptomyces : S. lipmaniiS. clavuligerusS. lactamdurans
![Page 29: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/29.jpg)
![Page 30: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/30.jpg)
Sifat:
-spektrum luas-Toksisitas rendah- ~ ampisilin- resisten thd penisilin beta laktamase- rentan thd cephalosporin beta laktamase
![Page 31: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/31.jpg)
Biosintesis:
[lisin] rendah
Produksi ningkat
![Page 32: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/32.jpg)
![Page 33: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/33.jpg)
Metode Produksi : mirip produksi penisilin
-fase pertumbuhan biomassa 90 jam-Spi 90 jam konsumsi O2 tinggi perlu aerasi tinggi-90 – 160 jam konsumsi O2 rendah-pH 7-Suhu 25 – 28 C-Medium : - corn steep liquor
- meat meal- sukrosa, glukosa- amonium asetat
Fermentasi:
Scr kimia: - dari penisilinharga penisilin rendah
![Page 34: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/34.jpg)
β-laktam baru:turunan semisintetik
-Nokardisin: - monosiklik β-laktam- efektif pd Gram –- Nocardia uniformis- Streptomyces alcalophilus
-As Klavulanat:- β-laktam-oxazolidin- kurang efektif- inaktivasi β-laktamase ireversibel- Streptomyces clavuligens- aplikasi kombinasi aktivitas ningkat
-Thienamisin : - β-laktam-pyrrolin- efektif pd Gram – & +- inaktivasi β-laktamase- Streptomyces cattleya- syw tidak stabil dikembangkan stabilitas
![Page 35: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/35.jpg)
Atb as. Amino & peptida:Turunan as. Amino : - sikloserin
- azoserinβ-laktamChromopeptidaDepsipeptidaLinier & siklik peptida
D-sikloserin: D-4-amino-3-isoxazolidonealami & sintetis
- S. orchidoceus- S. lavendulae- S. garyphalus- S. roseochromogenes
- Hambat sintesis dinding sel hambat alanin racemase- enzim produksi alanin
-efektif thd mycobacterium M. tubercolosis-Utk TBC; kombinasi dg isotinat hidrazin & rifampisin or streptomisin
![Page 36: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/36.jpg)
Aktinomisin: atb chromopeptida
-fenoksazon-kromoforunit dg pentapeptida-laktonas. Amino bervaryasi
-hambat RNA polimerase-Sangat toksik rusak liver & ginjal-Utk tumor/kanker
![Page 37: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/37.jpg)
Biosintesis:
![Page 38: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/38.jpg)
Atb depsipeptida: Subunit: as. Aminoas. hidroksil
# Valinomisin: - nilai ekonomi rendah- digunakan pd penelitian biokimia
hambat fosforilasi oksidatifcarrier K+
- S. fulvissimus
![Page 39: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/39.jpg)
# Virginiamisin:- efektif Gram +- pemicu pertumbuhan ternak unggas, babi, sapi- S. virginiae
![Page 40: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/40.jpg)
Atb peptida linier & siklik:
-MO : Bacillus sebagian besar atb peptidaStreptomyces
-BM : 270 – 4500-Sebagian besar siklik- di Bacillus produksi saat sporulasi
berperan dalam proses sporulasi-Aplikasi: terbatas toksik obat luar
- Gramisidin- Tirosidin- Basitrasin- polimiksin infeksi Gram –- viomisin- Capreonisin
Luka & luka bakar
TBC
![Page 41: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/41.jpg)
![Page 42: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/42.jpg)
Basitrasin:
-nilai ekonomi penting-Produksi th 1976 + 500 ton-Obat luar dan makanan ternak-Bacillus lincheniformis-Aktivitas hambat sintesis dinding sel
sintesis peptidoglikan
Biosintesis:tidak melibatkan ribosom, mRNA, & tRNAkomplek multienzim dinamakan:
“MESIN THIOTEMPLATE”ATP & Mg2+
A : BM 200 000B : BM 210 000C: BM 380 000
![Page 43: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/43.jpg)
“MESIN THIOTEMPLATE”
![Page 44: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/44.jpg)
Metode produksi:
![Page 45: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/45.jpg)
Atb Karbohidrat: Turunan gula & glikosida
![Page 46: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/46.jpg)
Nojirimisin:efektif thd Sarcina lutea & Xanthomonas oryzaeaktif menghambat α & β glukosidase dan amilase
![Page 47: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/47.jpg)
Atb Karbohidrat:
Efektif pd Gram –Utk infeksi akutToksik kerusakan ginjalEfek samping: kurang pendengaran
![Page 48: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/48.jpg)
![Page 49: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/49.jpg)
![Page 50: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/50.jpg)
Streptomisin:
Aktivitas : 1. Hambat sintesis proteinikat unit 12S dari subunit 30 Ssalah kode & baca12 S situs aktif pengikatan aminoakil-tRNA &
tMet-tRNA
2. Rusak membran sel hambat translokasi peptidil-tRNAkebocoran molekul BM kecil
Biosintesis: banyak enzim yg diketahui tapibelum dimengerti benar
![Page 51: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/51.jpg)
![Page 52: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/52.jpg)
Metode produksi:
-fermentasi : 150 000 lsuhu 28 – 30 CpH 7waktu 4 – 7 harisumber C : pati/dekstrinsumber N : soy meal
![Page 53: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/53.jpg)
![Page 54: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/54.jpg)
Atb makrosiklik lakton:
Efektif pd Gram +Hambat sintesis protein
ikat subunit ribosom 50 SS. erythreus
-Eritromisin
![Page 55: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/55.jpg)
![Page 56: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/56.jpg)
![Page 57: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/57.jpg)
Metode produksi:
-fermentasi submerged: glukosa 50 g/lsoy meal 30 g/l(NH4)2SO4 3 g/lNaCl 5 g/lCaCO3 6 g/lpH 7
![Page 58: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/58.jpg)
Tetrasiklin:
Struktur dasar cincin naftalenaPengguanaan luasSpektrum luas: Gram +, -, riketsia,
mycoplasma, spiroket, klamidiaAktivitas: hambat sintesis protein
subunit 30S: hambat ikatan aminoakil-tRNAke situs A ribosom
-aplikasi : - manusia- veteriner- ternak: unggas, babi- pengawetan : daging, unggas, ikan
![Page 59: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/59.jpg)
![Page 60: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/60.jpg)
![Page 61: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/61.jpg)
![Page 62: Mikroba Penghasil Antibiotik - · PDF fileMenghambat sintesis peptidoglikan. Ætarget: transpeptidase & D-alanin karboksipeptidase. Polimerase peptidoglikan terhambat. ÆHambat sel](https://reader033.vdocuments.net/reader033/viewer/2022050901/5a72c3277f8b9a9d538de9ae/html5/thumbnails/62.jpg)
Pengembangan:
Rekayasa genetik ?
-Transformasi Streptomyces-Antibiotik baru
???