PHYSICAL MUTAGENESIS BASED STRAIN IMPROVEMENT OF ASPERGILLUS SP. FOR ENHANCED PRODUCTION OF LOVASTATIN

Authors

  • R. S. Upendra Sr. Assistant Professor, Dept. of Biotechnology, New Horizon College of Engineering, Outer ring road, Bellandur post, Marathahalli, Bangalore -560103, Karnataka, India
  • Pratima Khandelwal

Keywords:

Aspergillus terreus, Lovastatin, UV Random Mutations, Strain Improvement, Submerged fermentation

Abstract

Objective: The present investigation aimed towards the strain improvement of lovastatin maximum yielding wild-type fungal strains (Aspergillus terreus-MTCC 11045, Aspergillus terreus-MTCC 11395 and Aspergillus flavus-MTCC 11396) through physical mutagenesis by applying UV random mutations.

Methods: Revival of fungal cultures on PDA plates followed by a screening of their morphological and microscopic properties. Strain improvement of screened fungi by UV (255 nm) random mutagenesis, selection of mutants based on morphological variations further submerged fermentation of selected (SmF) mutants, subsequently extraction of lovastatin from the spent broth and the extracts were analyzed for the presence of lovastatin by TLC and UV spectrophotometer scans (200-300 nm).

Results: Out of eighteen screened mutant samples seven showed positive results for the lovastatin production. Among these seven positive cultures, Aspergillus terreus 11045-90 found to yield the maximum amount of lovastatin (3912 mg/l).

Conclusion: The present study concludes by reporting the evidence of raised in the lovastatin titre by three-fold compared to the yield of the wild-type strain (996 mg/l) and confirms the achievement of strain improvement by UV random mutagenesis.

Keywords: Aspergillus terreus, Lovastatin, UV Random mutations, Strain improvement, Submerged fermentation

Downloads

Download data is not yet available.

References

Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, et al. Mevinolin: a highly potent competitive inhibitor of hydroxymethyl glutaryl coenzyme A reductase and cholesterol lowering agent. Proc NAS U S A 1980;77:3957–61.

Kaneko I, Hazame, Shimada Y, Endo A. Inhibitory effects on lipid metabolism in cultured cells of ML-236B, a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase. Eur J Biochem 1978;87:317-21.

http://www.webmd.com/drugs/2/drug-11594-92/lovastatin-oral/lovastatin-oral/details. [Last accessed on 10 Feb 2016].

Klawitter J, Touraj Shokati, Vanessa Moll, Uwe Christians, Jost Klawitter. Effects of lovastatin on breast cancer cells: a proteo-metabonomic study. Breast Cancer Res 2010;12:R16.

Camelia Stancu, Floarea Serbancea, Gabriela Botez, Anca Sima. The hypocholesterolemic effect of probiotics in the hyperlipidemic hamster. Proc Rom Acad Ser B: Chem Life Sci Geosci 2008;3:145–14.

Olivera Stojadinovic, Elizabeth Lebrun, Irena Pastar, Robert Kirsner, Stephen C Davis, Marjana Tomic-Canic. Statins as potential therapeutic agents for healing disorders. Expert Rev Dermatol 2010;5:689-98.

Greenwood J, Walters CE, Pryce G, Kanuga N, Beraud E, Baker D, et al. Lovastatin inhibits brain endothelial cell Rho-mediated lymphocyte migration and attenuates experimental autoimmune encephalomyelitis. FASEB J 2003;17:905-7.

Upendra RS, Pratima Khandelwal, Amiri ZR, Swetha L, Mohammed Ausim S. Screening and molecular characterization of natural fungal isolate producing lovastatin. J Microb Biochem Technol 2013;5:25-30.

Upendra RS, Pratima Khandelwal, ZR Amiri, Aparna S, Archana C, Ashwathi M. Isolation and Characterization of lovastatin producing grade food fungi from oriental foods. World J Pharm Res 2014;3:1404-14.

Devi Sree K, Venkateswara Rao J, Lakshmi Narasu M, SaiKrishna K. Isolation and screening of lovastatin-producing Aspergillus terreus fungal strains from soil samples. Int J Pharmacol Ther 2011;3:2772-82.

Gabriela B, Valter V, Adela V, Jana G. A method of fermentation preparation of lovastatin by an Aspergillus terreus strain and the strain for performing the method. Patent; 1999.

L´opez Casas JL, JA S´anchez P´erez, JM Fern´andez Sevilla, EM Rodr´ıguez Porcel, Y Chisti. Pellet morphology, culture rheology and lovastatin production in cultures of Aspergillus terreus. J Biotechnol 2004;116:61–77.

Upendra RS, Pratima Khandelwal, ZR Amiri,Baboo M Nair. The invited session key lecture on Optimization of a process for producing lovastatin from novel fungal isolatesâ€. Proc SUTPBM; 2014. p. 28-34.

Jaivel N, P Marimuthu. Optimization of lovastatin production in solid state fermentation (SSF) by Aspergillus terreus. Int J Eng Sci Res Technol 2010;2:2730-3.

Pratima Khandelwal, Upendra RS, Vivek R, Nandhini NJ. Optimization of parameters for lovastatin production using a high yielding strain of GRAS fungi, and development of novel (geriatric) foods for its delivery as a means of cognitive and preventive health care. Proc Food Processing Technologies-Challenges & Solution for Sustainable Food Security; 2013. p. 197.

Atalla MM, Hamed ER, El-Shami AR. Optimization of a culture medium for increased mevinolin production of Aspergillus terreus strain. Malays J Microbiol 2008;4:6-10.

Osman ME, OH Khattab, GM Zaghlol, Rehab M, Abd El-Hameed. Optimization of some physical and chemical factors for lovastatin productivity by a local strain of Aspergillus terreus. Afr J Basic Appl Sci 2011;5:718-32.

Vilches Ferron MA, JL Casas Lopez, JA Sanchez Perez, JM Fernandez Sevilla, Y Chisti. Rapid screening of Aspergillus terreus mutants for over production of lovastatin. World J Microbiol Biotechnol 2005;21:123–5.

Harleen Kaur, Amarjeetkaur, HS Saini, BS Chadha. Screening and selection of lovastatin hyper-producing mutants of A. terreus using cyclic mutagenesis. Acta Microbiol Immunol Hung 2009;56:167–78.

Jaivel N, P Marimuthu. Strain improvement of Aspergillus terreus for increased lovastatin production. Int J Eng Sci Res Technol 2010;2:2612-5.

Upendra RS, Pratima K, Swetha, Manaswini. Molecular characterizations of the lovastatin-producing fungal isolate. Organism-Aspergillus terreus SSM4. Gen Bank; 2013.

Upendra RS, Pratima K. Isolation and molecular characterization of natural fungal isolates producing lovastatin. Organism-Aspergillus terreus SSM3. Gen Bank; 2013.

Upendra RS, Pratima K. Molecular characterizations of the lovastatin-producing fungal isolate. Organism-Aspergillus flavus SSM8. Gen Bank; 2013.

Upendra RS, Pratima K, Ausim M. Molecular characterization of lovastatin-producing fungal isolates. Organism-Rhizopus oryzae SSM9. Gen Bank; 2013.

Siamak, M Samiee, Nasrin Moazami, Saeid Haghighi, Farzaneh Aziz Mohseni, Saeid Mirdamadi, et al. Screening of lovastatin production by filamentous fungi. Iran Biomed J 2003;7:29-33.

Hajko P, A Wildman. Process for the purification of HMG-CoA reductase inhibitors. U. S. Patent; 1993.

Upendra RS, Khandelwal P. Mohammed ausim: a novel approach for enhancement of Lovastatin production using Aspergillus species. Proc SUPBT; 2012. p. 135-40.

Upendra RS, Khandelwal P, Mohammed Ausim. A novel approach for enhancement of Lovastatin production using Aspergillus species. Int J Agric Environ Biotechnol 2013;6:779-86.

Sreedevi K, Venkateswara Rao J, Lakshmi Narasu, Fareedullah Md. Strain improvement of Aspergillus terreus for the enhanced production of lovastatin, an HMG-COA reductase inhibitor. J Microbiol Biotechnol Res 2011;1:96-100.

Published

01-07-2016

How to Cite

Upendra, R. S., and P. Khandelwal. “PHYSICAL MUTAGENESIS BASED STRAIN IMPROVEMENT OF ASPERGILLUS SP. FOR ENHANCED PRODUCTION OF LOVASTATIN”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 7, July 2016, pp. 163-7, https://journals.innovareacademics.in/index.php/ijpps/article/view/11488.

Issue

Section

Original Article(s)