Biosintesis Senyawa Obat (Fa-4206)

8/13/2019 Biosintesis Senyawa Obat (Fa-4206)

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BIOSINTESIS SENYAWA OBAT(FA-4206)

Marlia Singgih WibowoMarlia Singgih Wibowo

School of Pharmacy ITBSchool of Pharmacy ITB


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Pendahuluanendahuluan

AturanAturan kuliahkuliah :: kehadirankehadiran,, performaperformamahasiswamahasiswa

UTS, UAS,UTS, UAS, tugastugas,, presentasipresentasi

PartisipasiPartisipasi didi kelaskelas

SilabusSilabus

DaftarDaftarPustaka/BukuPustaka/BukuAcuanAcuan


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ISI KULIAHSI KULIAH

PendahuluanPendahuluan MikroorganismeMikroorganisme penghasilpenghasil bahanbahan obatobat

BiosintesisBiosintesis

dalamdalam

MikroorganismeMikroorganisme

TeknologiTeknologi fermentasifermentasi

ContohContoh produksiproduksi bahanbahan obatobat asalasal

mikroorganismemikroorganisme


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Sumberumber alamlam senyawaenyawa obatbat

TanamanTanaman ((simplisiasimplisia,, ekstrakekstrak,, isolatisolat,,metabolit/eksudatmetabolit/eksudat,, senyawasenyawa aktifaktif))

HewanHewan ((bagianbagian organ,organ, ekstrakekstrak organ,organ,

metabolit/eksudatmetabolit/eksudat,, senyawasenyawa aktifaktif))

Mineral (Mineral (bahanbahan tambangtambang

MikroorganismeMikroorganisme ((biomassabiomassa,, metabolitmetabolit,,senyawasenyawa pemandupemandu,, senyawasenyawa aktifaktif))


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Cauliflower fungiCauliflower fungi


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Pemanfaatanemanfaatan mikroorganismeikroorganisme BiomassaBiomassa

EnzimEnzim

MetabolitMetabolit primerprimer

MetabolitMetabolit sekundersekunder

BiotransformasiBiotransformasi

BioinformatikBioinformatik TugasTugas : min.5: min.5 manfaatmanfaat mikroorganismemikroorganisme didi

bidangbidang farmasifarmasi (2 weeks)(2 weeks)


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KuliahKuliah22

Proses pembuatan obat


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Prosesroses pembuatanembuatan obatbat SintesisSintesis kimiakimia ((parasetamolparasetamol, aspirin,, aspirin,

salbutamolsalbutamol,, dlldll))

SemiSemi sintesissintesis ((lead compoundlead compound daridari alamalam,, lalulalumodifikasimodifikasi strukturstruktursecarasecara kimiakimia)) contohcontoh ::tetrasiklintetrasiklin 66--deoksi 5deoksi 5--hidroksihidroksi tetrasiklintetrasiklin((doksisiklindoksisiklin))

BiosintesisBiosintesis ((senyawasenyawa aktifaktifdaridari alamalam)) contohcontoh ::vitamin Bvitamin B1212 daridari Pseudomonas spPseudomonas sp

RekayasaRekayasa GenetikaGenetika


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PendapatPendapatparaparaahliahli

OrbitalsOrbitals are for mathematiciansare for mathematicians -- OrganicOrganicchemistry is for people who likes to cook!chemistry is for people who likes to cook! --

AlexanderAlexander ShulginShulgin When I was young I played withWhen I was young I played with legoslegos, but now, but now

I am older and I play with atomsI am older and I play with atoms -- SynesthesiaSynesthesia

There is more space between atoms, thanThere is more space between atoms, thanthere are atoms in the universe...there are atoms in the universe... -- ZodiacZodiacYouthYouth

The flask is your canvas and the periodic chartThe flask is your canvas and the periodic chartyour paletteyour palette -- RatHeadRatHead

Chemistry is lifeChemistry is life -- Everything else is just waitingEverything else is just waiting

-- Uncle AlUncle Al


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The pharmaceutical industry is unquestionably vibrantThe pharmaceutical industry is unquestionably vibranttoday, with drug synthesis making a vital contribution.today, with drug synthesis making a vital contribution.Whether in the early developmental stages ofWhether in the early developmental stages ofidentifying and optimizing a lead, or the latter stages ofidentifying and optimizing a lead, or the latter stages of

process development and costprocess development and cost --effective scaleeffective scale--up, theup, theabili ty to design elegant and economical syntheticabili ty to design elegant and economical syntheticroutes is often a major factor in the eventual viabilityroutes is often a major factor in the eventual viabilityand commercial success of a drug.and commercial success of a drug.

Contemporary Drug Synthesis examines how leadingContemporary Drug Synthesis examines how leadingresearchers and manufacturers have integratedresearchers and manufacturers have integratedchemistry, biology, pharmacokinetics, and a host ofchemistry, biology, pharmacokinetics, and a host ofother disciplines in the creation and development ofother disciplines in the creation and development of

leading drugs. Authored by four of the pharmaceuticalleading drugs. Authored by four of the pharmaceuticalindustryindustrys most respected scientists, this timelys most respected scientists, this timelyvolume:volume:

Focuses on the processes that resulted in highFocuses on the processes that resulted in high--profileprofile

drugs includingdrugs including LipitorLipitor,, CelebrexCelebrex, Viagra,, Viagra, GleevecGleevec,,NexiumNexium, Clarit in, and over a dozen others, Clarit in, and over a dozen others

Chemical synthesis for Drug Substances


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Provides an inProvides an in--depth introduction to eachdepth introduction to eachdrug, followed by a detailed account of itsdrug, followed by a detailed account of its

synthesissynthesis Organizes the drugs into fourteen therapeuticOrganizes the drugs into fourteen therapeutic

areas for clarity and ease of useareas for clarity and ease of use

Process chemists provide an essential bridgeProcess chemists provide an essential bridgebetween chemistry and the marketplace,between chemistry and the marketplace,creating scientifically practical drugcreating scientifically practical drug

processes while never losing sight of theprocesses while never losing sight of thecommercial viability of those processes.commercial viability of those processes.

Contemporary Drug Synthesis meets theContemporary Drug Synthesis meets theneeds of a growing community of researchersneeds of a growing community of researchers

in pharmaceutical research and development,in pharmaceutical research and development,and is both a useful guide for practicingand is both a useful guide for practicingpharmaceutical scientists and an excellentpharmaceutical scientists and an excellent

text for medicinal and organic chemistrytext for medicinal and organic chemistrystudents.students.


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JenisJenisobatobat


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BiosintesisBiosintesis

ProsesProses sintesissintesis yangyang terjaditerjadi padapada makhlukmakhluk

hiduphidup untukuntuk menghasilkanmenghasilkan metabolitmetabolit primerprimerdandan atauatau metabolitmetabolit sekundersekunder

MetabolitMetabolit primer :primer : hasilhasil metabolismemetabolisme yangyangdigunakandigunakan untukuntuk kelangsungankelangsungan hiduphidup

((prosesproses tumbuhtumbuh),), contohcontoh :: asamasam amino,amino,

asetilasetil CoACoA,, gulagula--gulagula,, nukleotidanukleotida,, asamasamsitratsitrat,, dandan lainlain--lainlain


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MetabolitMetabolit sekundersekunder:: hasilhasil metabolismemetabolisme yangyang

tidaktidak digunakandigunakan untukuntuk prosesproses pertumbuhanpertumbuhan,,

tetapitetapi misalnyamisalnya untukuntuk pertahananpertahanan diridiri,, contohcontoh ::

protein,protein, asamasam lemaklemak,, karbohidratkarbohidrat,, senyawasenyawaantimikrobaantimikroba,, dandan lainlain--lainlain

PadaPadajalurjalurbiosintesisbiosintesis metabolitmetabolit sekundersekunderdapatdapat

terdiriterdiri daridari berbagaiberbagaijalurjalur,, mulaimulai daridari yangyangsederhanasederhana sampaisampai dengandenganjalurjaluryangyang rumitrumit


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MetabolitMetabolitsekundersekunder

UmumnyaUmumnya berasalberasal atauatau berawalberawal daridarimetabolitmetabolit primer (primer (asetilasetil coAcoA,, asamasammevalonatmevalonat,, asamasam sikimatsikimat,, dlldll))

UnikUnik untukuntuk setiapsetiap mikroorganismemikroorganisme,,bergantungbergantung padapada lingkunganlingkungan habitatnyahabitatnya

ContohContoh metabolitmetabolit sekundersekunderdaridarimikroorganismemikroorganisme :: antibiotikantibiotik,, pigmenpigmen,,

vitamin,vitamin, dandan lainlain--lainlain


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BeberapaBeberapacontohcontohmetabolitmetabolit

sekundersekundermikrobamikrobadandanmanfaatnyamanfaatnya

AntibiotikAntibiotik :: penisilinpenisilin ((PenicilliumPenicillium chrysogenumchrysogenum),),

sefalosporinsefalosporin ((CephalosporiumCephalosporium acremoniumacremonium),),

ImunosupresanImunosupresan :: silosporinsilosporin ((TrichodermaTrichoderma

polysoprumpolysoprum)) BidangBidang pertanianpertanian : growth promoter: growth promoter

ZearalononeZearalonone ((GibberellaGibberella zeaezeae))

EnzimEnzim :: amilaseamilase ((AspergillusAspergillus nigerniger), lipase), lipase

((PseudomonasPseudomonas aeruginosaaeruginosa))

PigmenPigmen :: ankaflavinankaflavin ((MonascusMonascus purpureuspurpureus))


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PembentukanPembentukaneritromisineritromisin


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Metabolitetabolit sekunderekunder mikrobaikroba yangangmerupakanerupakan senyawaenyawa toksikoksik

ToksinToksin daridari fungifungi mikotoksinmikotoksin,, contohcontoh ::

aflatoksinaflatoksin ((AspergillusAspergillus flavusflavus),), sitrininsitrinin

((PenicilliumPenicillium citrinumcitrinum))

ToksinToksin daridari bakteribakteri

bakterotoksinbakterotoksin,, contohcontoh ::endotoksinendotoksin

DapatDapat dimanfaatkandimanfaatkan untukuntuk merancangmerancang obatobat

berdasarkanberdasarkan strukturstrukturmolekulmolekul toksintoksin


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MetabolitMetabolitsekundersekunderuntukuntukpertahananpertahanandiridiri

atauataukompetisikompetisidengandenganmikrobamikrobalainlain


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PenicilliumPenicilliumdidiatasatasselaiselaimenghasilkanmenghasilkanpatulinpatulin,, senyawasenyawa

yang palingyang paling awalawaldirancangdirancanguntukuntukmenjadimenjadiantibiotikantibiotik,,

tetapitetapiternyataternyatatoksiktoksikuntukuntukmamaliamamalia

Struktur Patulin


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Aflatoksinflatoksin B11Aflotoxins are produced inmembers of the Aspergillus

parasiticus group via the

polyketide pathway. The

pathway has around 20 steps,and the end products include a

diversity of related compounds

(bisfuranocoumarins) that can

be readily converted one toanother


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BiomakromolekulBiomakromolekul

PadaPada umumnyaumumnya metabolitmetabolit sekundersekundermikroorganismemikroorganisme merupakanmerupakanmakromolekulmakromolekul yangyang disebutdisebut

biomakromolekulbiomakromolekul MikroorganismeMikroorganisme yangyang dimanfaatkandimanfaatkan atauatau

dimanipulasidimanipulasi agaragar menghasilkanmenghasilkan produkproduk

yangyang bermanfaatbermanfaat dandan dapatdapat diproduksidiproduksidalamdalam skalaskala industriindustri disebutdisebut mikrobamikrobaindustriindustri


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Mikroorganisme Mikrobaikroorganisme Mikroba Industrindustri ProkariotProkariot ((EubakteriEubakteri,,ArchaebakteriArchaebakteri))

EukariotEukariot (Fungi :(Fungi :KapangKapang,, RagiRagi,, JamurJamur;;

Algae, Protozoa)Algae, Protozoa)

PatogenPatogen dandan nonnon--patogenpatogen

PemanfaatanPemanfaatan dalamdalam bioteknologibioteknologi klasikklasik

dandan bioteknologibioteknologi modernmodern


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akteriakteri BerdasarkanBerdasarkan strukturstrukturdindingdinding selsel :: bakteribakteri

gram (+)gram (+) dandan gram (gram (--))

BerdasarkanBerdasarkan sifatsifat selsel :: eubacteriaeubacteria,,

filamentous bacteria,filamentous bacteria, archaebacteriaarchaebacteria,,photosynthetic bacteriaphotosynthetic bacteria

StreptomycesStreptomyces merupakanmerupakan kelompokkelompokbakteribakteri yang palingyang paling banyakbanyak dimanfaatkandimanfaatkan

metabolitmetabolit sekundernyasekundernya didi bidangbidang farmasifarmasi


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ungiungi KapangKapang ((jamurjamurberfilamenberfilamen))

RagiRagi (yeast)(yeast)

Mushroom (Mushroom (jamurjamurbertudungbertudung))

KapangKapang yangyang seringsering dimanfaatkandimanfaatkan ::

AscomycotaAscomycota,, DeuteromycotaDeuteromycota


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PustakaPustakatentangtentangmetabolitmetabolit

sekundersekunderfungifungi Cox RJ (2007)Cox RJ (2007) The biosynthesis ofThe biosynthesis of polyketidespolyketides,, acylacyl

tetramictetramic acids andacids and pyridonespyridones by filamentous fungi. In:by filamentous fungi. In:Exploitation of FungiExploitation of Fungi EdsEds Robson GD, van West P &Robson GD, van West P &GaddGadd GM CUP.GM CUP.

Griffin DH (1994)Griffin DH (1994) Fungal PhysiologyFungal Physiology. Wiley, New York.. Wiley, New York.

Hocking AD & Pitt JI (1996)Hocking AD & Pitt JI (1996) Fungi andFungi and mycotoxinsmycotoxins ininfood. In: Fungi of Australiafood. In: Fungi of Australia. 1B, 315. 1B, 315 342.342.

Mann J. (1986)Mann J. (1986) Secondary MetabolismSecondary Metabolism. OUP, Oxford.. OUP, Oxford.

ViningVining

LC (1990)LC (1990)

Functions of secondary metabolitesFunctions of secondary metabolites

.

.Annual review of Microbiology 44, 395Annual review of Microbiology 44, 395 427.427.

Yu JYu J--H & Keller N. (2005)H & Keller N. (2005) Regulation of secondaryRegulation of secondarymetabolism in filamentous fungimetabolism in filamentous fungi. Annual Review of. Annual Review of

PhytopathologyPhytopathology 43: 43743: 437--458.458.

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Biosintesis Senyawa Obat (Fa-4206)