BIOKONVERSI SEFALOSPORIN C MENJADI ASAM 7-AMINOSEFALOSPORANAT DENGAN SEFALOSPORIN ASILASE
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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 megaterium, Aeromonas sp., dan Arthrobacter. Aktivitas CPC asilase alami sangat rendah dan rekayasa genetik digunakan untuk meningkatkan aktivitasnya.
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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