Abstract
Rifamycin is a broad-spectrum antimicrobial drug produced commercially by submerged fermentation where the yields are far less in comparison to its demand in human drug therapy. Addressing the need, sequential mutational strain improvement was carried using UV and EtBr that resulted in improved strain yielding rifamycin SV up to 4.32 g/L. Further optimization of six important fermentation factors was followed which include temperature, agitation, inoculum level, period of fermentation, inorganic nitrogen source and amino acids. For the first time, we report a maximum yield of 5.32 g/L of rifamycin SV. Among the amino acids, proline known for its slowest assimilation by Amycolatopsis mediterranei produced the highest improvement in antibiotic yields. Following mutational strain improvement and process optimization, a total of 3.8-fold increase in antibiotic titre was achieved. Following a conventional procedure of mutational strain improvement, highest yield of rifamycin SV was reported by optimizing submerged fermentation process.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aruna A, Nagavalli M, Girijashankar V, Venkateswar Rao L (2015) Direct bio-ethanol production by amylolytic yeast Candida albicans. Lett Appl Microbiol. doi:10.1111/lam.12348
Bapat PM, Bhartiya S, Venkatesh KV, Wangikar PP (2005) Structured kinetic model to represent the utilization of multiple substrates in complex media during rifamycin B fermentation. Biotechnol Bioeng 93:779–790
Bapat PM, Debasish Das, Sujata VS, Wangikar PP (2006) Hierarchical amino acid utilization and its influence on fermentation dynamics: rifamycin B fermentation using Amycolatopsis mediterranei S699, a case study. Microb Cell Factories 5(32):1–14
Demain AL (1992) Microbial secondary metabolism: a new frontier for academia a new opportunity for industry. In: Derek J Chadwick Julie Whelan (ed) Secondary Metabolites: Their functions and role. CIBA Foundation, London, 18–20 February, Wiley, pp 3–16
El-Tayeb OM, Salama AA, Hussein MMM, El-Sedawy HF (2004) Optimization of industrial production of rifamycin B by Amycolatopsis mediterranei. III. Production in fedbatch mode in shake flasks. African J Biotech 3(8):387–394
Ellaiah P, Srinivasulu B, Adinarayana K (2004) Optimisation studies on neomycin production by a mutant strain of Streptomyces marinensis in solid state fermentation. Process Biochem 39:529–534
Floss HG, Yu TW (2005) Rifamycin-mode of action resistance and biosynthesis. Chem Rev 105:621–632
Ghisalba O, Auden JAL, Schupp T, Nuesch J (1994) The rifamycins properties. Biosynthesis and fermentation. In: Vandamme E (ed) Biotechnology of industrial antibiotics. Maecel Decker Inc, New York, pp 281–327
Kim CG, Yu TW, Fryhle BC, Sandeep H, Floss HG (1998) 3-Amino-5-hydroxybenzoic acid synthase the terminal enzyme in the formation of the precursor of mC7N units in rifamycin and related antibiotics. J Biol Chem 273:6030–6040
Lal R, Lal S (1994) Recent trends in rifamycin research. Bioessays 16:211–216
Lee H, Song M, Hwang S (2003) Optimizing bioconversion of deproteinated cheese whey to mycelia of Ganoderma lucidum. Process Biochem 38:1685–1693
Ma FX, Kim JH, Kim SB, Seo YG, Chang YK, Hong SK, Kim CJ (2008) Medium optimization for enhanced production of rifamycin B by Amycolatopsis mediterranei S699: combining a full factorial design and a statistical approach. Process Biochem 43:954–960
Mahalaxmi Y, Subba Rao C, Suvarnalaxmi G, Satish T, Sudhakar P, Prakasham RS (2008) Rifamycin B production pattern in Nocardia RSP-3 strain and influence of barbital on antibiotic production. Curr Trends Biotechnol Pharmacol 2(1):173–181
Mahalaxmi Y, Sathish T, Prakasham RS (2009) Development of balanced medium composition for improved rifamycin B production by isolated Amycolatopsis sp. RSP-3. Lett Appl Microbiol 49:533–538
Murali Krishna PS, Venkateswarlu G, Venkateswar Rao L (2000) Effect of uracil on rifamycin SV production by Amycolatopsis mediterranei MV35R. Lett Appl Microbiol 31:73–76
Nagavalli M, Ponamgi SPD, Girijashankar V, Venkateswar Rao L (2015) Solid state fermentation and production of rifamycin SV using Amycolatopsis mediterranei. Lett Appl Microbiol 60:44–51
Pasha C, NagaValli M, Rao LV (2007) Lanta camara for fuel ethanol production using thermotolerant yeast. Lett Appl Microbiol 44(6):666–672
Pasqualucci CR, Vigevani V, Radaelli P, Gallo GG (1970) Improved differential spectrophotometric determination of rifamycins. J Pharm Sci 59:685–687
Peela S, Ponamgi D, Mandali N, Terli R (2012) Mutation induced enhanced production of novel antibiotic SBR-22 by Streptomycess psammoticus BT-408 (MTCC- 4902). J Pharm Res 5(8):4480–4483
Rakesh Vohra M, Dube S (1989) Identification and quantitation of rifamycins by reversed-phase high-performance liquid chromatography. J Chromatogr 477:463–466
Rana F (2013) Rifampicin—an overview. Int J Res Pharm Chem 3(1):83–87
Venkateswarlu G, Murali Krishna PS, Venkateswar Rao L (1999) Production of rifamycin using Amycolatopsis mediterranei (MTCC14). Bioprocess Eng 20:27–30
Venkateswarlu G, Murali PS, Sharma G, Rao LV (2000) Improvement of rifamycin B production using mutant strains of Amycolatopsis mediterranei. Bioprocess Eng 23(4):315–318
Author information
Authors and Affiliations
Corresponding author
Additional information
All authors carry equal weightage.
Rights and permissions
About this article
Cite this article
Nagavalli, M., Ponamgi, S.P.D., Girijashankar, V. et al. Enhanced rifamycin SV production by submerged fermentation using Amycolatopsis mediterranei . Appl Microbiol Biotechnol 99, 7505–7513 (2015). https://doi.org/10.1007/s00253-015-6682-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-015-6682-2