Tylosin

Improvement of tylosin A production yields by engineering of the producer strain

01.05.2018 bis 31.10.2019

Tylosin is a 16-membered macrolide antibiotic used as veterinary medicine to treat infections caused by Gram-positive bacteria. The antibiotic is produced by diverse Streptomyces species, including Streptomyces fradiae, Streptomyces rimosus, and Streptomyces hygroscopicus. The material enriched from fermentation cultures of a producer strain and the formulated products are composed of tylosin factor-A or tylosin-A (80–90%), and small amounts of factors B, C, and D (4). All components contribute to the potency of tylosin. However, tylosin A is the major agent (usually about 90% and not less than 80%), which provides the antibacterial activity. Although, several biosynthetic mutants of S. fradiae were obtained, either by classical mutagenesis approaches or directed genetic manipulation, and the biosynthetic steps are relatively well studied, there are reactions of which mechanisms remain unexplored (e.g. the degradation of tylosin A to tylosin D). As tylosin A is the main component exhibiting the highest activity against Gram-positive pathogens, the investigation and understanding of the tylosin A degradation process is of particular interest. The obtained knowledge will provide opportunities for strategy development enabling the generation of strain-derivatives producing tylosin A as sole product or in which the degradation of tylosin A is reduced.
Therefore, a non-engineered producer will be modified to a high-producer strain for a “straightforward” production and detection of tylosin and subsequently utilized to investigate the tylosin A degradation process and further improve the strain performance by elimination or inhibition of tylosin A degradation.