Enhanced Production of Sisomicin in Micromonospora inyoensis by Protoplast Mutagenesis and Fermentation Optimization

Area of Science:

• Microbiology
• Biotechnology
• Fermentation Science

Background:

• Sisomicin, a key aminoglycoside antibiotic and precursor to netilmicin and plazomicin, suffers from low fermentation yields.
• Limited production restricts the broader application of sisomicin and its clinically significant derivatives.

Purpose of the Study:

• To significantly improve sisomicin production through strain breeding and fermentation optimization.
• To achieve the highest possible fermentation titer for sisomicin.

Main Methods:

• Chemical mutagenesis of Micromonospora inyoensis OG-1 using diethyl sulfate on protoplasts.
• Screening for high-yielding, genetically stable mutant strains.
• Optimization of carbon and nitrogen sources and dissolved oxygen levels in fermentation.

Main Results:

• A high-yielding mutant strain (H6-32) was developed, increasing sisomicin titer by 42.6% to 1486 U·mL^-1.
• Optimized fermentation conditions, including dissolved oxygen control, yielded a final sisomicin titer of 1780 U·mL^-1.
• Comparative genome analysis identified 13 gene mutations in the high-yielding strain H6-32.

Conclusions:

• The study successfully developed a high-yielding sisomicin strain and optimized fermentation, achieving a record titer.
• This work provides a valuable reference for future strain development and fermentation process optimization in antibiotic production.
• The findings contribute to a deeper understanding of the genetic basis of sisomicin overproduction.