Improved doramectin production based on high-throughput screening and medium optimization in Streptomyces avermitilis

Area of Science:

• Microbiology and Biotechnology
• Drug Discovery and Development
• Fermentation Technology

Background:

• Doramectin is a key macrocyclic lactone antibiotic for treating mammalian parasitic diseases.
• Current production methods yield low doramectin, insufficient for industrial demand.
• Improving doramectin yield is crucial for its widespread application.

Purpose of the Study:

• To develop a high-yield mutant strain of Streptomyces avermitilis for enhanced doramectin production.
• To optimize fermentation conditions for maximizing doramectin yield.
• To establish a scalable and efficient method for industrial doramectin fermentation.

Main Methods:

• High-throughput screening of Streptomyces avermitilis mutants using plasma mutagenesis and tolerance-based selection.
• Optimization of fermentation medium using response surface methodology.
• Scale-up of fermentation in a 50 L fermenter.

Main Results:

• A high-yield mutant strain, S. avermitilis DA-137, was identified, increasing doramectin production by 187% (431.5 mg/L).
• Optimized fermentation medium further boosted yield to 934.5 mg/L in shake flasks.
• The highest reported doramectin yield of 1217 mg/L was achieved in a 50 L fermenter.

Conclusions:

• Mutagenesis combined with high-throughput screening is an effective strategy for enhancing doramectin production.
• Medium optimization significantly improves doramectin yield in Streptomyces avermitilis fermentation.
• This study provides a valuable reference for increasing yields of macrocyclic lactone antibiotics.