eris septiana, Martha Sari, Siti Irma Rahmawati, Fauzia Nurul Izzati, Rikno Harmoko, Apon Zaenal Mustopa



Penicillium chrysogenum is one of the fungi which known to produce penicillin G antibiotics. The current superior strain P. chrysogenum producing high penicillin G has gone through various stages from the wild type isolates. The wild type isolates of P. chrysogenum from Indonesia also have great potential to be developed. Therefore, this study aimed to determine the changes of penicillin G levels from mutated P. chrysogenum isolate with both ultraviolet (UV) radiation and chemical mutagens ethyl methane sulfonate (EMS) compared to the wild type isolates. Random mutation through UV radiation, EMS chemical mutagen and their combination was carried out on wild type isolates of P. chrysogenum. Antibacterial activity was tested against Escherichia coli and Bacillus subtilis. The level of penicillin G produced was detected using HPLC with the Penicillin G as the standard. The results showed that the treatment of UV, EMS mutations and their combination can increase the antibacterial activity as well as levels of penicillin G than the wild type. Mutant C5-4.10 isolate resulted from the combination UV and EMS had the best antibacterial activity and produced penicillin G. level 2.9 times compared to the wild type.

Keywords: antibiotic, HPLC, mutation, Penicillium chrysogenum, penicillin G


Penicillium chrysogenum adalah salah satu kapang yang diketahui memproduksi antibiotik penisilin G. Strain P. chrysogenum unggul penghasil penisilin G tinggi yang saat ini tersedia merupakan galur yang telah melalui berbagai tahapan pemuliaan dari wild type-nya. Isolat P. chrysogenum asal Indonesia juga memiliki potensi besar untuk dikembangkan. Oleh karena itu, penelitian ini bertujuan untuk mengetahui perubahan kadar penisilin G dari isolat P. chrysogenum yang telah dimutasikan menggunakan radiasi sinar ultraviolet (UV) dan mutagen kimiawi etil metan sulfonat (EMS) dibandingkan dengan wild type nya. Mutasi acak menggunakan radiasi sinar UV, mutagen kimiawi EMS dan kombinasi keduanya dilakukan pada isolat P. chrysogenum. Uji aktivitas antibakteri dilakukan terhadap Escherichia coli dan Bacillus subtilis. Kadar penisilin G yang diproduksi dideteksi menggunakan HPLC dan dibandingkan dengan standar Penicillin G. Hasil penelitian menunjukkan bahwa mutasi menggunakan sinar UV, EMS dan kombinasi keduanya dapat meningkatkan aktivitas antibakteri serta kadar penisilin G dibandingkan dengan wild type nya. Isolat mutan C5-4.10 hasil mutasi kombinasi sinar UV dan EMS memiliki aktivitas antibakteri terbaik dan kadar penisilin G sebesar 2,9 kali lipat dibandingkan dengan wild type nya.

Kata kunci: antibiotik, HPLC, mutasi, Penicillium chrysogenum, penisilin G


antibiotic; HPLC; mutation; Penicillium chrysogenum; penicillin G

Full Text:



Brakhage, A. A. (1998). Molecular regulation of β-lactam biosynthesis in filamentous fungi. Microbiology and Molecular Biology Reviews, 62, 547-585.

CLSI. (2012). Performance Standards for Antimicrobial Disk Susceptibility Tests. 11st Ed. CLSI standard M02. Pennsylvania: Clinical and Laboratory Standards Institute.

Elander, R. P. (2003). Industrial production β-lactam antibiotics. Applied Microbiology and Biotechnology, 61, 385-392.

Gerea, A. L., Branscum, K. M., King, J. B., You, J., Powell, D. R., Miller, A. N., Spear, J. R., & Cichewicz, R. H. (2012). Secondary metabolites produced by fungi derived from a microbial mat encountered in an iron-rich natural spring. Tetrahedron Letters, 53, 4202-4205.

Hardianto, D., Suyanto, Prabandari, E. E., Windriawati. L., Marwanta, E., & Tarwadi. (2015). Penicillin production by mutant of Penicillium chrysogenum. Jurnal Bioteknologi & Biosains Indonesia, 2, 61-65.

Harris, D. M., Van der Kroght, Z. A., Klaassen, P., Raamsdonk, L. M., Hage, S., Van den Berg, M., Bovenberg, R. A. L., Pronk, J. T., & Daran, J-M. (2009). Exploring and dissecting genome-wide gene expression responses of Penicillium chrysogenum to phenylacetic acid consumption and penicillin G production. BMC Genomics, 10, 75.

Lehtinen, J., & Lilius, E. M. (2007). Promethazine renders Eschrichia coli susceptible to penicillin G: real-time measurement of bacterial susceptibility by fluoro-luminometry. International Journal of Antimicrobial Agents, 30, 44-51.

Leimbach, A., Hacker, j., & Dobrindt, U. (2013). E. coli as an all-rounder: the thin line between commensalism and pathogenicity. Current Topics in Microbiology and Immunology, 358, 3-52.

Lieberman, M. (2018). HPLC methodology manual: Distributed pharmaceutical analysis laboratory. Indiana: Department of chemistry and biochemistry, University of Notre Dame.

Mohd-Yusoff, N. F., Ruperao, P., Tomoyoshi, N. E., Edwards, D., Gresshoff, P. M., Biswas, B., & Batley, J. (2015). Scanning the effects of ethyl methanesulfonate on the whole genome of Lotus japonicus using second-generation sequencing analysis. G3 (Bethesda), 5, 559-567.

Onyegeme-Okerenta, B. M., Chinedu, S. N., Okafor, U. A., & Okochi, V. I. (2009). Antibacterial activity of culture extracts of Penicillium chrysogenum PCL501: effects of carbon sources. Online Journal of Health Allied Sciences, 8, 1-9.

Onyegeme-Okerenta, B. M., Okochi, V. I., & Chinedu, S. N. (2013). Penicillin production by Penicillium chrysogenum PCL 501: effect of UV induced mutation. Internet Journal of Microbiology, 12, 1-7.

Parekh, S., Vinci, V. A., & Strobel, R. J. (2000). Improvement of microbial strain and fermentation processes. Applied Microbiology and Biotechnology, 54, 287-301.

Pramisandi, A., Sunaryanto, R., Suyanto, & Prabandari, E. E. (2012). Effect of phenylacetic acid addition on productivity of Penicillium chrysogenum in penicillin G production using pilot scale reactor. In Widayat, L. Buchori, N. A. Handayani (Eds.), 1st International Conference on Chemical and Material Engineering (pp. BRE.15 1-6). Semarang: Diponegoro University.

Rachman, S. D., Safari, A., Fazli, Kamara, D. S., Sidik, A., Udin, L. Z., & Ishmayana, S. (2016). Produksi penisilin oleh Penicillium chrysogenum L112 dengan variasi kecepatan agitasi pada fermentor 1L. Kartika-Jurnal Ilmiah Farmasi, 4, 1-6.

Radha, S., Babul, R. H., Sridevi, A., Prasad, N. B. L., & Narashima, G. (2012). Development of mutant fungal strain of Aspergillus niger for enhanced production of acid protease in submerged and solid state fermentation. European Journal of Experimental Biology, 2, 1517-1528.

Rajeshkumar, J., Ilyas, M. H. M. (2011). Production of phosphatase by mutated fungal strains. International Multidisiplinary Research Journal, 1, 23-29.

Rochette, P. J., Lacoste, S., Therrien, J. P., Bastien, N., Brash, D. E., & Drouin, R. (2009). Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA. Mutation Research, 665, 7-13.

Soares, G. M. S., Figueiredo, L. C., Faveri, M., Cortelli, S. C., Duarte, P. M., & Feres, M. (2012). Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs. Journal of Applied Oral Science, 20, 295-309.

Syafriana, V., Nuswantara, S., Mangunwardoyo, W., & Lisdiyanti, P. (2014). Enhancement of β-glucosidase activity in Penicillium sp. by random mutation with ultraviolet and ethyl methyl sulfonate. Annales Bogorienses, 18, 27-33.

Thykaer, J., & Nielsen, J. (2003). Metabolic engineering of beta-lactam production. Metabolic Engineering, 5, 56-69.

Veerapagu, M., Jeya, K. R., & Ponmurugan, K. (2008). Mutational effect of Penicillium chrysogenum on antibiotic production. Short communication. Advanced BioTechnology, 8, 16-19.

White, S., Berry, D. R., & McNeil, B. (1999). Effect of phenylacetic acid feeding on the process of cellular autolysis in submerged batch cultures of Penicillium chrysogenum. Journal of Biotechnology, 75, 173-185.

Wiese, J., & Imhoff, J. F. (2018). Marine bacteria and fungi as promising source for new antibiotics. Drug Development Research, 80, 24-27.

Wiharyanti, R., Hardianto, D., Kusumaningrum, H. P., & Budiharjo, A. (2014). Kloning gen pcbC dari Penicillium chrysogenum ke dalam plasmid pPICZA untuk pengembangan produksi penisilin G. BIOMA, 16, 33-38.

Zhu, T. F., Chen, F. F., & Li, J. C. (2017). A strain of pathogenic Bacillus subtilis results in brain damage in ducklings when co-infected with Riemerella anatipestifer. Polish Journal of Veterinary Sciences, 20, 803-809.

Ziemons, S., Koutsantas, K., Becker, K., Dahlmann, T., & Kuck, U. (2017). Penicillin production in industrial strain Penicillium chrysogenum P2niaD18 is not dependent on the copy number of biosynthesis genes. BMC Biotechnology, 17, 16.



  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.


Published by :

Institute for Industrial Research and Standardization (Baristand Industri) in Pontianak

Agency for Industrial Research and Development, Ministry of Industry 

Jl. Budi Utomo No. 41 Pontianak, West Kalimantan, Indonesia

Tel / Fax : +62 561 881393, 881533

email      :


BIOPROPAL Industri indexed in: 

Hasil gambar untuk gambar doajHasil gambar untuk gambar google scholar

RJI Main logo