Upstream and Downstream Processing of Lovastatin by Aspergillus terreus

• Published in: Cell biochemistry and biophysics Vol. 70; no. 1; pp. 309 - 320
• Main Authors: Mukhtar, Hamid, Ijaz, Syeda Sidra, Ikram-ul-Haq
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2014; Springer Nature B.V
• Subjects: Air flow; Aspergillus - drug effects; Aspergillus - genetics; Aspergillus - metabolism; Aspergillus - radiation effects; Aspergillus terreus; Batch Cell Culture Techniques; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Bioreactors - microbiology; Biotechnology; Carbon - metabolism; Carbon sources; Cell Biology; Fermentation; Flow rates; Hydrogen-Ion Concentration; Life Sciences; Lovastatin - biosynthesis; Lovastatin - chemistry; Lovastatin - isolation & purification; Mutagenesis - drug effects; Mutagenesis - radiation effects; Mutants; Nitrogen - metabolism; Nitrous Acid - pharmacology; Original Paper; Pharmacology/Toxicology; Solvent extraction; Temperature; Time Factors; Ultraviolet Rays; X-ray diffraction; Lipid lowering; Mutagenesis; Fermentation; Crystal analysis; Downstream processing
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-014-9914-7

The present study describes the enhanced production and purification of lovastatin by Aspergillus terreus in submerged batch fermentation. The enhancement of lovastatin production from A. terreus was attempted by random mutagenesis using ultraviolet radiations and nitrous acid. UV mutants exhibited increased efficiency for lovastatin production as compared with nitrous acid mutants. Among all the mutants developed, A. terreus UV-4 was found to be the hyper producer of lovastatin. This mutant gave 3.5-fold higher lovastatin production than the wild culture of A. terreus NRRL 265. Various cultural conditions were also optimized for hyper-producing mutant strain. 5 % glucose as carbon source, 1.5 % corn steep liquor as nitrogen source, initial pH value of 6, 120 h of incubation period, and 28 °C of incubation temperature were found as best parameters for higher lovastatin production in shake flasks. Production of lovastatin by wild and mutant strains of A. terreus was also scaled up to laboratory scale fermentor. The fermentation process was conducted at 28 °C, 200 rpm agitation, and 1vvm air flow rate without pH control. After the optimization of cultural conditions in 250 ml Erlenmeyer flasks and scaling up to laboratory scale fermentor, the mutant A. terreus UV-4 gave eightfold higher lovastatin production (3249.95 μg/ml) than its production by wild strain in shake flasks. Purification of lovastatin was carried out by solvent extraction method which yielded 977.1 mg/l of lovastatin with 98.99 % chromatographic purity and 26.76 % recovery. The crystal structure of lovastatin was determined using X-ray diffraction analysis which is first ever reported.