Upstream and downstream processing of lovastatin by Aspergillus terreus

Area of Science:

• Microbiology
• Biotechnology
• Biochemistry

Background:

• Lovastatin, a cholesterol-lowering drug, is produced by Aspergillus terreus.
• Enhancing lovastatin yield through microbial strain improvement and fermentation optimization is crucial for industrial applications.

Purpose of the Study:

• To improve lovastatin production by Aspergillus terreus via random mutagenesis.
• To optimize fermentation conditions for enhanced lovastatin yield.
• To purify and characterize the produced lovastatin.

Main Methods:

• Random mutagenesis of Aspergillus terreus using UV radiation and nitrous acid.
• Screening and selection of hyper-producing lovastatin mutants.
• Optimization of cultural parameters (carbon source, nitrogen source, pH, temperature, incubation time) in shake flasks.
• Scale-up of fermentation in a laboratory fermentor.
• Purification of lovastatin using solvent extraction.
• Characterization of purified lovastatin using X-ray diffraction analysis.

Main Results:

• UV mutagenesis generated a hyper-producing mutant, A. terreus UV-4, yielding 3.5-fold higher lovastatin than the wild type.
• Optimized conditions (5% glucose, 1.5% corn steep liquor, pH 6, 28°C, 120h) significantly boosted lovastatin production.
• Scale-up in a fermentor resulted in an eightfold increase in lovastatin production (3249.95 μg/ml) compared to wild strain in shake flasks.
• Purification yielded 977.1 mg/l lovastatin with 98.99% purity and 26.76% recovery.
• The crystal structure of lovastatin was determined for the first time.

Conclusions:

• Strain improvement through UV mutagenesis is effective for enhancing lovastatin production.
• Fermentation optimization and scale-up are critical for maximizing lovastatin yield.
• The study successfully produced and purified high-purity lovastatin, with its crystal structure elucidated.