Liu Gang's research group significantly increased the production of bleomycin in Streptomyces verticillium through gene cluster precision multiplication technology

Bleomycin is a PKS/NRPS hybrid broad-spectrum anti-tumor antibiotic produced by Streptomyces verticillium and has been used in the treatment of clinical malignant tumors
.

The yield of bleomycin in its original producing bacteria is extremely low, and its production level needs to be improved urgently
.

However, the genetic manipulation of Streptomyces verticillium is difficult, and there are few reports that the production of bleomycin has been greatly increased by rational means
.

Recently, Liu Gang's research group from the Institute of Microbiology of the Chinese Academy of Sciences published a research paper entitled "Remarkable enhancement of bleomycin production through precise amplification of its biosynthetic gene cluster in Streptomyces verticillus" in Science China Life Sciences, which was significantly improved through gene cluster precision multiplication technology.
The production of bleomycin in Streptomyces verticillium was measured
.

In this research, Liu Gang's research group successfully constructed a high-frequency multiplication system containing ZouA system in Streptomyces verticillium, and used the apramycin resistance gene (aac(3)IV) and catechol 2,3 -The double reporter gene system composed of dioxygenase gene (xylE) can detect the multiplication efficiency of gene clusters
.

Through high-frequency multiplication based on the ZouA system under resistance-enriched culture conditions and high-throughput screening of the dual reporter gene system, recombinant strains containing 1-6 copies of the bleomycin biosynthetic gene cluster were obtained
.

The recombinant strains containing 1-6 copies of the bleomycin biosynthesis gene cluster were fermented and cultured, and it was found that the yield of bleomycin A2 increased with the increase of the copy number of the gene cluster, while the yield of bleomycin B2 did not change.
Obviously
.

Finally, the production of bleomycin in the recombinant strain IMS51 containing 6 copies of the gene cluster was increased to 9.
59 times that of the original strain, indicating that the doubling of the biosynthetic gene cluster can effectively increase the production of bleomycin in Streptomyces verticillium
.

Significantly increase the production of bleomycin in Streptomyces verticillium through gene cluster precision multiplication technology.
This study provides a quick and efficient tool for increasing the production of antibiotics in Streptomyces through biosynthetic gene cluster multiplication
.

Li Hong, a doctoral student at the Institute of Microbiology, Chinese Academy of Sciences, is the first author of the article, and researcher Liu Gang is the corresponding author
.

For details of the research, please read the original text▼[click the link below or read the original text] Li, H.
, Gao, W.
, Cui, Y.
, Pan, Y.
, and Liu, G.
(2021).
Remarkable enhancement of bleomycin production through precise amplification of its biosynthetic gene cluster in Streptomyces verticillus.
Sci China Life Sci 64, https://doi.
org/10.
1007/s11427-021-1998-8