BIOKONVERSI SEFALOSPORIN C MENJADI ASAM 7-AMINOSEFALOSPORANAT DENGAN SEFALOSPORIN ASILASE

Main Article Content

Dudi Hardianto
Bima Wedana Isdiyono
Fransiskus Xaverius Ivan

Abstract

Sefalosporin merupakan antibiotik golongan β-laktam yang paling banyak digunakan di dunia dan secara klinis aktif terhadap bakteri gram positif dan gram negatif. Sefalosporin C merupakan sefalosporin alami yang dihasilkan oleh kapang Cephalosporium acremonium. Sefalosporin C mempunyai aktivitas antibakteri moderat dengan nilai konsentrasi hambat minimum 25-100 µg/mL untuk bakteri gram positif dan 12-25 µg/mL untuk bakteri gram negatif. Sefalosporin C dapat diubah menjadi asam 7-aminosefalosporanat (7-ACA) sebagai senyawa antara untuk pembuatan turunan sefalosporin dengan metode enzimatik secara dua atau satu tahap. Produksi 7-ACA secara enzimatik dapat menggunakan metode dua tahap dan satu tahap enzimatik. Metode enzimatik secara dua tahap menggunakan enzim asam D-amino oksidase (DAAO) untuk menghasilkan asam glutaril-7-aminosefalosporinat (GL-7-ACA) pada tahap pertama dan menggunakan asam glutaril-7-aminosefalosporinat asilase untuk menghasilkan 7-ACA pada tahap kedua. Metode enzimatik secara satu tahap menggunakan sefalosporin asilase untuk mengubah CPC menjadi 7-ACA secara langsung. Beberapa mikroorganisme penghasil sefalosporin asilase yaitu Pseudomonas sp., Bacillus megateriumAeromonas sp., dan Arthrobacter. Aktivitas CPC asilase alami sangat rendah dan rekayasa genetik digunakan untuk meningkatkan aktivitasnya.

Article Details

How to Cite
Hardianto, D., Isdiyono, B. W., & Ivan, F. X. (2023). BIOKONVERSI SEFALOSPORIN C MENJADI ASAM 7-AMINOSEFALOSPORANAT DENGAN SEFALOSPORIN ASILASE. Jurnal Bioteknologi Dan Biosains Indonesia, 3(2), 89–95. Retrieved from https://ejournal.brin.go.id/JBBI/article/view/1878
Section
Review

References

Barber MS, Giesecke U, Reichert A, Minas W (2004) Industrial enzymatic production of cephalosporin-based β-lactams. Adv Biochem Eng Biotechnol 88:179-215

Egorov AM, Kurochkina VB, Sklyarenko AV, Nys PS (2000) Enzymatic transformation of betalactam antibiotics: Trend of development and approaches to practical implementation. Biocatalysis Fundament Appl 41:43-46

Elander RP (2003) Industrial production of β-lactam antibiotic. Appl Microbiol Biotechnol 61:385-392. Doi: 10.1007/s00253-003-1274-y

Gaurav K, Kundu K, Kundu S (2010) Biosynthesis of cephalosporin-C acylase enzyme: optimal media design, purification, and characterization. Artif Cells Blood Substit Immobil Biotechnol 38:277-283. Doi: 10.3109/10731199.2010.482036

Golden E, Paterson R, Tie WJ, Anandan A, Flematti G, Molla G, Rosini E, Pollegioni L, Vrielink A (2013) Structure of a class III engineered cephalosporin acylase: comparisons with class I acylase and implications for differences in substrate specificity and catalytic activity. Biochem J 451:217-226. Doi: 10.1042/BJ20121715

Jobanputra AH, Vasait RD (2015) Cephalosporin C acylase from Pseudomonas species: production and enhancement of its activity by optimization of process parameters. Biocatal Agric Biotechnol 4:465-470. Doi: 10.1016/j.bcab.2015.06.009

Kim Y, Yoon KH, Khang Y, Turley S, Hol WGJ (2000) The 2.0 Å crystal structure of cephalosporin acylase. Structure 8:1059-1068. Doi: 10.1016/S0969-2126(00)00505-0

Li Q, Huang X, Zhu Y (2014) Evaluation of active designs of cephalosporin C acylase by molecular dynamics simulation and molecular docking. J Mol Model 20:2314. Doi: 10.1007/s00894-014-2314-5

Nupura H, Asmita T, Sharath B, Asmita P (2008) Media optimization for the production of cephalosporin C acylase from a novel bacterial source: Alcaligenes xylosoxidans MTCC*491. Res J Biotechnol 3:16-21

Oh B, Kim M, Yoon J, Chung K, Shin Y, Lee D, Kim Y (2003) Deacylation activity of cephalosporin acylase to cephalosporin C is improved by changing the side-chain conformations of active-site residues. Biochem Biophys Res Commun 310:19-27. Doi:10.1016/j.bbrc.2003.08.110

Pollegioni L, Lorenzi S, Rosini E, Marcone GL, Molla G, Verga R, Cabri W, Pilone MS (2005) Evolution of an acylase active on cephalosporin C, Protein Sci 14:3064-3076. Doi: 10.1110/ps.051671705

Pollegioni L, Rosini E, Molla G (2013) Cephalosporin C acylase: dream and(/or) reality. Appl Microbiol Biotechnol 97:2341-2355. Doi: 10.1007/s00253-013-4741-0

Ren Y, Lei Y, Zhu Y (2014) Site-directed mutagenesis of cephalosporin c acylase and enzymatic conversion of cephalosporin C to 7-aminocephalosporanic acid. Turk J Biochem 39:51-56. Doi: 10.5505/tjb.2014.48569

Shin YC, Jeon JYJ, Jung KH, Park MR, Kim Y (2009) Cephalosporin C acylase mutant and method for preparing 7-aca using same. Patent US 7592168 B2

Sio CF (2004) Mutants and homologs of cephalosporin acylase: for antibiotics and antibiosis. Thesis, Rijksuniversiteit Groningen

Sonawane VC (2006) Enzymatic modifications of cephalosporins by cephalosporin acylase and other enzymes. Crit Rev Biotechnol 26:95-120. Doi: 10.1080/07388550600718630

Vasait RD, Jobanputra AH (2015) Single step bioconversion of cephalosporin C by strain of Achromobacter species isolated from rhizosphere soil. Adv Biores 6:124-127. Doi: 10.15515/abr.0976-4585.6.3.124127

Xiao Y, Huo X, Qian Y, Zhang Y, Chen G, Ouyang P, Lin Z (2014) Engineering of a CPC acylase using a facile pH indicator assay. J Ind Microbiol Biotechnol 41:1617-1625. Doi: 10.1007/s10295-014-1501-9

Yau MH, Wang J, Tsang PW, Fong WP (2006) J1 acylase, a glutaryl-7-aminocephalosporanic acid acylase from Bacillus laterosporus J1, is a member of the alpha/beta-hydrolase fold superfamily. 580:1465-1471. Doi: 10.1016/j.febslet.2006.01.069

Yu R (2013) Modeling and experimental analysis of cephalosporin C acylase and its mutant. The Open Biotechnol J 7:30-37. Doi: 10.2174/1874070701307010030

Zhang J, Yu H, Wang Y, Luo H, Shen Z (2014) Determination of the second autoproteolytic cleavage site of cephalosporin C acylase and the effect of deleting its flanking residues in the α-C-terminal region. J Biotechnol 184:138-145. Doi: 10.1016/j.jbiotec.2014.05.016