Engineered bacteria producing terramycin, and construction method and application thereof

By integrating the oxytetracycline biosynthesis gene cluster into Streptomyces white Del14 and enhancing otcR expression, the problems of difficult genetic manipulation and long cycle in oxytetracycline synthesis in industrial Streptomyces were solved, achieving efficient OTC production with a yield of 1.1 g/L.

CN116804179BActive Publication Date: 2026-07-24INST OF MICROBIOLOGY CHINESE ACAD OF SCI
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Patent Information

Application Number
CN202210272631.3
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-03-18
Publication Date
2026-07-24
Estimated Expiration
2042-03-18

AI Technical Summary

Technical Problem

The genetic manipulation of oxytetracycline synthesis in existing industrial streptomyces is difficult and time-consuming, and there is an urgent need for a low-cost and efficient method to increase yield.

Method used

Using Streptomyces albopictus Del14 as the chassis strain, the oxytetracycline biosynthesis gene cluster was integrated through plasmid introduction or genetic engineering, and the expression of the gene otcR within the cluster was enhanced to construct an engineered strain. This process included adding a strong promoter, knocking out the negative regulatory factor otrR, and replacing the integrase site to optimize the OTC synthesis pathway.

Benefits of technology

The heterogeneous and efficient synthesis of OTC was achieved, with a yield of 1.1 g/L, which shortened the production cycle and improved production efficiency, demonstrating the potential of Streptomyces albopictus Del14 as a chassis for OTC production.

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Abstract

The application provides an engineered oxytetracycline-producing bacterium and a construction method and application thereof. The application takes Streptomyces albus Del14 as a chassis production strain, and successfully expresses an otc cluster in S.albus Del14 for the first time through heterologous reconstitution. Specifically, the otc cluster is expressed by increasing one copy of otcR started by a strong promoter PkasO*; the efflux of OTC is improved by knocking out a negative regulatory factor OtrR in the cluster to release the repression on otrB; further, an efficient OTC production chassis Del14B::oxy1KΔotrR is screened out by replacing an integrase site, and the OTC yield of the chassis Del14B::oxy1KΔotrR reaches 1.1 g / L on the 6th day, which is equivalent to the yield of the original production strain S.rimosus M4018 on the 8th day, so that the heterologous efficient synthesis of OTC is realized.
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