Volume 9, Issue 4 (2018)                   JMBS 2018, 9(4): 571-578 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Jaberi Ansari F, Jalili H. Effect of Spore Age and Inducers on Lovastatin Production in Aspergillus terreus. JMBS 2018; 9 (4) :571-578
URL: http://biot.modares.ac.ir/article-22-16584-en.html
1- Medical Nanotechnology Department, Advanced Technologies in Medicine Faculty, Tehran University of Medical Sciences, Tehran, Iran
2- Life Science Engineering Department, New Sciences & Technologies Faculty, University of Tehran, Tehran, Iran, New Sciences & Technologies Faculty, University of Tehran, Kargar Shomali Street, Tehran, Iran. , hjalili@ut.ac.ir
Abstract:   (3534 Views)
Aims: One of the ways to reduce cholesterol is to use statins that prevent cholesterol synthesis. The statins are similar to mevalonate and act as a competitive inhibitor of HMG-CoA reductase enzyme. Lovastatin is the eminent derivate of the statins group, which is produced by many microorganisms. At commercial scale lovastatin is produced in submerged culture by Aspergillus terreus. The industrial production of this metabolite is carried out by Aspergillus turosus in liquid culture. The main aim of this research was to investigate the effect of spore age on lovastatin production at the inoculation stage; also, the impact of adding olive oil and tetracycline as inducers for lovastatin production were examined.
Materials and Methods: In the present experimental research, different suspensions from varying ages of spore were prepared and added to the medium of Aspergillus terreus ATCC 20542; lovastatin concentration also was measured by High Performance Liquid Chromatography (HPLC).
Findings: The utmost lovastatin was observed in inoculum with 85 days spore age and equal to 60 mg/l, which was approximately twice higher compared to when inoculated with 10 days spore age. The best concentration of spore inoculation was 0.5×107 spores/ml. Lovastatin production significantly increased when tetracycline and olive oil were used as inducers.
Conclusion: As the inoculated spore age increases, lovastatin and biomass production is increased. The lovastatin production is increases by more than 1.5 times while adding tetracycline and olive oil compared to date syrup alone.
Full-Text [PDF 362 kb]   (3915 Downloads)    
Article Type: _ | Subject: Agricultural Biotechnology
Received: 2017/04/23 | Accepted: 2018/02/18 | Published: 2018/12/21

1. Gunde-Cimerman N, Friedrich J, Cimerman A, Benički N. Screening fungi for the production of an inhibitor of HMG CoA reductase: Production of mevinolin by the fungi of the genus Pleurotus. FEMS Microbiol Lett. 1993;111(2-3):203-6. [Link] [DOI:10.1111/j.1574-6968.1993.tb06386.x]
2. Subazini TK, Kumar GR. Characterization of lovastatin biosynthetic cluster proteins in aspergillus terreus strain ATCC 20542. Bioinformation. 2011;6(7):250-4. [Link] [DOI:10.6026/97320630006250]
3. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, et al. Mevinolin: A highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci U S A. 1980;77(7):3957-61. [Link] [DOI:10.1073/pnas.77.7.3957]
4. Endo A, Kuroda M, Tanzawa K. Competitive inhibition of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase by ML‐236A and ML‐236B fungal metabolites, having hypocholesterolemic activity. FEBS Lett. 1976;72(2):323-6. [Link] [DOI:10.1016/0014-5793(76)80996-9]
5. Endo A, Kuroda M, Tsujita Y. ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogensis produced by Penicillium citrinum. J Antibiot (Tokyo). 1976;29(12):1346-8. [Link] [DOI:10.7164/antibiotics.29.1346]
6. Jůzlová P, Martínková L, Křen V. Secondary metabolites of the fungusMonascus: A review. J Ind Microbiol. 1996;16(3):163-70. [Link] [DOI:10.1007/BF01569999]
7. Casas López JL, Sánchez Pérez JA, Fernández Sevilla JM, Acién Fernández FG, Grima EM, Chisti Y. Production of lovastatin by Aspergillus terreus: Effects of the C: N ratio and the principal nutrients on growth and metabolite production. Enzyme Microb Technol. 2003;33(2-3):270-7. [Link] [DOI:10.1016/S0141-0229(03)00130-3]
8. Goswami S, Vidyarthi AS, Bhunia B, Mandal T. A review on lovastatin and its production. J Biochem Technol. 2012;4(1):581-7. [Link]
9. Hajjaj H, Niederberger P, Duboc P. Lovastatin biosynthesis by Aspergillus terreus in a chemically defined medium. Appl Enviro Microbiol. 2001;67(6):2596-602. [Link] [DOI:10.1128/AEM.67.6.2596-2602.2001]
10. Sitaram Kumar M, Jana SK, Senthil V, Shashanka V, Vijay Kumar S, Sadhukhan AK. Repeated fed-batch process for improving lovastatin production. Process Biochem. 2000;36(4):363-8. [Link] [DOI:10.1016/S0032-9592(00)00222-3]
11. Manzoni M, Bergomi S, Rollini M, Cavazzoni V. Production of statins by filamentous fungi. Biotechnol Lett. 1999;21(3):253-7. [Link] [DOI:10.1023/A:1005495714248]
12. Manzoni M, Rollini M, Bergomi S, Cavazzoni V. Production and purification of statins from Aspergillus terreus strains. Biotechnol Tech. 1998;12(7):529-32. [Link] [DOI:10.1023/A:1008851430560]
13. Novak N, Gerdin S, Berovic M. Increased lovastatin formation by Aspergillus terreus using repeated fed-batch process. Biotechnol Lett. 1997;19(10):947-8. [Link] [DOI:10.1023/A:1018322628333]
14. Prasanna Latha D, Hemalatha KPJ. Production of lovastatin by Aspergillus fischeri NCIM 509 using barley bran, wheat husk, rice bran and rice husk under solid state fermentation. Eur J Exp Biol. 2015;5(8):8-17. [Link]
15. Porcel ER, López JL, Ferrón MA, Pérez JA, Sánchez JL, Chisti Y. Effects of the sporulation conditions on the lovastatin production by Aspergillus terreus. Bioprocess Biosyst Eng. 2006;29(1):1-5. [Link] [DOI:10.1007/s00449-006-0048-1]
16. Ehgartner D, Fricke J, Schröder A, Herwig C. At-line determining spore germination of Penicillium chrysogenum bioprocesses in complex media. Appl Microbiol Biotechnol. 2016;100(20):8923-30. [Link] [DOI:10.1007/s00253-016-7787-y]
17. Bizukojc M, Gonciarz J. Influence of oxygen on lovastatin biosynthesis by Aspergillus terreus ATCC 20542 quantitatively studied on the level of individual pellets. Bioprocess Biosyst Eng. 2015;38(7):1251-66. [Link] [DOI:10.1007/s00449-015-1366-y]
18. Wang B, Chen J, Li H, Sun F, Li Y, Shi G. Pellet-dispersion strategy to simplify the seed cultivation of Aspergillus niger and optimize citric acid production. Bioprocess Biosyst Eng. 2017;40(1):45-53. [Link] [DOI:10.1007/s00449-016-1673-y]
19. Lai LS, Hung CS, Lo CC. Effects of lactose and glucose on production of itaconic acid and lovastatin by Aspergillus terreus ATCC 20542. J Biosci Bioeng. 2007;104(1):9-13. [Link] [DOI:10.1263/jbb.104.9]
20. Atkinson S, Williams P. Quorum sensing and social networking in the microbial world. J R Soc Interface. 2009;6(40):959-78. [Link] [DOI:10.1098/rsif.2009.0203]
21. Raina S, De Vizio D, Palonen EK, Odell M, Brandt AM, Soini JT, et al. Is quorum sensing involved in lovastatin production in the filamentous fungus Aspergillus terreus?. Process Biochem. 2012;47(5):843-52. [Link] [DOI:10.1016/j.procbio.2012.02.021]
22. Waters CM, Bassler BL. Quorum sensing: Cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319-46. [Link] [DOI:10.1146/annurev.cellbio.21.012704.131001]
23. Sorrentino F, Roy I, Keshavarz T. Impact of linoleic acid supplementation on lovastatin production in Aspergillus terreus cultures. Appl Microbiol Biotechnol. 2010;88(1):65-73. [Link] [DOI:10.1007/s00253-010-2722-0]
24. Brown SH, Scott JB, Bhaheetharan J, Sharpee WC, Milde L, Wilson RA, et al. Oxygenase coordination is required for morphological transition and the host-fungus interaction of Aspergillus flavus. Mol Plant Microbe Interact. 2009;22(7):882-94. [Link] [DOI:10.1094/MPMI-22-7-0882]
25. Horowitz Brown S, Zarnowski R, Sharpee WC, Keller NP. Morphological transitions governed by density dependence and lipoxygenase activity in Aspergillus flavus. Appl Environ Microbiol. 2008;74(18):5674-85. [Link] [DOI:10.1128/AEM.00565-08]
26. Tsitsigiannis DI, Keller NP. Oxylipins act as determinants of natural product biosynthesis and seed colonization in Aspergillus nidulans. Mol Microbiol. 2006;59(3):882-92. [Link] [DOI:10.1111/j.1365-2958.2005.05000.x]
27. Tsitsigiannis DI, Kowieski TM, Zarnowski R, Keller NP. Three putative oxylipin biosynthetic genes integrate sexual and asexual development in Aspergillus nidulans. Microbiology. 2005;151(Pt 6):1809-21. [Link] [DOI:10.1099/mic.0.27880-0]
28. Dartora AB, Bertolin TE, Bilibio D, Silveira MM, Costa JA. Evaluation of filamentous fungi and inducers for the production of endo-polygalacturonase by solid state fermentation. Zeitschrift für Naturforschung C. 2002;57(7-8):666-70. [Link] [DOI:10.1515/znc-2002-7-820]
29. Jaberi Ansari F, Jafari Mansoorian H, Jalili H, Azizi M. A review of the effective factors for lovastatin production by Aspergillus terreus ATCC 20542 in liquid submerged fermentation. J Babol Univ Med Sci. 2016;18(12):40-8. [Link]
30. Jia Z, Zhang X, Cao X. Effects of carbon sources on fungal morphology and lovastatin biosynthesis by submerged cultivation of Aspergillus terreus. Asia Pac J Chem Eng. 2009;4(5):672-7. [Link] [DOI:10.1002/apj.316]
31. Greenspan MD, Yudkovitz JB. Mevinolinic acid biosynthesis by Aspergillus terreus and its relationship to fatty acid biosynthesis. J Bacteriol. 1985;162(2):704-7. [Link]
32. Endo A. Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. J Antibiot (Tokyo). 1979;32(8):852-4. [Link] [DOI:10.7164/antibiotics.32.852]
33. Jaberi Ansari F, Hajihassan Z, Jalili H. Recombinant β-NGF production in E.coli using date syrup. Modares J Biotechnol. 2015;6(2):63-70. [Persian] [Link]
34. Vadakke Kamath P, Santebennur Dwarakanath B, Chaudhary A, Janakiraman S. Optimization of culture conditions for maximal lovastatin production by Aspergillus terreus (KM017963) under solid state fermentation. HAYATI J Biosci. 2015;22(4):174-80. [Link] [DOI:10.1016/j.hjb.2015.11.001]
35. Rahman NA, Hasan M, Hussain MA, Jahim J. Determination of glucose and fructose from glucose isomerization process by high performance liquid chromatography with UV detection. Mod Appl Sci. 2008;2(4):151-4. [Link] [DOI:10.5539/mas.v2n4p151]
36. Jia Z, Zhang X, Zhao Y, Cao X. Enhancement of lovastatin production by supplementing polyketide antibiotics to the submerged culture of Aspergillus terreus. Appl Biochem Biotechnol. 2010;160(7):2014-25. [Link] [DOI:10.1007/s12010-009-8762-1]
37. Karthika C, Sharmila G, Muthukumaran C, Manikandan K. Utilization of whey powder as an alternate carbon source for production of hypocholesterolemic drug by Aspergillus terreus MTCC 1281. Food Sci Biotechnol. 2013;22(5):1-7. [Link] [DOI:10.1007/s10068-013-0220-8]
38. Nielsen J, Johansen CL, Jacobsen M, Krabben P, Villadsen J. Pellet formation and fragmentation in submerged cultures of Penicillium chrysogenum and its relation to penicillin production. Biotechnol Prog. 1995;11(1):93-8. [Link] [DOI:10.1021/bp00031a013]
39. Bizukojc M, Ledakowicz S. Biosynthesis of lovastatin and (+)-geodin by Aspergillus terreus in batch and fed-batch culture in the stirred tank bioreactor. Biochem Eng J. 2008;42(3):198-207. [Link] [DOI:10.1016/j.bej.2008.06.022]
40. Bizukojc M, Ledakowicz S. Biosynthesis of lovastatin and (+)-geodin by Aspergillus terreus in batch and fed-batch culture in the stirred tank bioreactor. Biochem Eng J. 2008;42(3):198-207. [Link] [DOI:10.1016/j.bej.2008.06.022]
41. Abd Rahim MH. Production of lovastatin, (+)-geodin and sulochrin by Aspergillus terreus ATCC 20542 using pure and crude glycerol [Dissertation]. Sydney: The University of Sydney; 2015. [Link]
42. Jia Z, Zhang X, Zhao Y, Cao X. Effects of divalent metal cations on lovastatin biosynthesis from Aspergillus terreus in chemically defined medium. World J Microbiol Biotechnol. 2009;25(7):1235-41. [Link] [DOI:10.1007/s11274-009-0007-5]
43. Radha KV, Lakshmanan D. A review: Lovastatin production and applications. Asian J Pharm Clin Res. 2013;6(3):21-6. [Link]
44. Gonciarz J, Bizukojc M. Adding talc microparticles to Aspergillus terreus ATCC 20542 preculture decreases fungal pellet size and improves lovastatin production. Eng Life Sci. 2014;14(2):190-200. [Link] [DOI:10.1002/elsc.201300055]
45. Palonen EK, Neffling MR, Raina S, Brandt A, Keshavarz T, Meriluoto J, et al. Butyrolactone I quantification from lovastatin producing Aspergillus terreus using tandem mass spectrometry-evidence of signalling functions. Microorganisms. 2014;2(2):111-27. [Link] [DOI:10.3390/microorganisms2020111]
46. Kennedy J, Auclair K, Kendrew SG, Park C, Vederas JC, Hutchinson CR. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science. 1999;284(5418):1368-72. [Link] [DOI:10.1126/science.284.5418.1368]
47. Witter DJ, Vederas JC. Putative diels-alder-catalyzed cyclization during the biosynthesis of lovastatin. J Org Chem. 1996;61(8):2613-23. [Link] [DOI:10.1021/jo952117p]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.