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Identification of the streptothricin and tunicamycin biosynthetic gene clusters by genome mining in Streptomyces sp. strain fd1-xmd

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Abstract

The genus Streptomyces have been highly regarded for their important source of natural products. Combined with the technology of genome sequencing and mining, we could identify the active ingredients from fermentation broth quickly. Here, we report on Streptomyces sp. strain fd1-xmd, which was isolated from a soil sample collected in Shanghai. Interestingly, the fermentation broth derived from this strain demonstrated broad-spectrum antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and eukaryotes. To identify the antimicrobial substances and their biosynthetic gene clusters, we sequenced the fd1-xmd strain and obtained a genome 7,929,999 bp in length. The average GC content of the chromosome was 72.5 mol%. Knockout experiments demonstrated that out of eight biosynthetic gene clusters we could identify, two are responsible for the biosynthesis of the antibiotics streptothricin (ST) and tunicamycin (TM). The ST biosynthetic gene cluster from fd1-xmd was verified via successful heterologous expression in Streptomyces coelicolor M1146. ST production had a yield of up to 0.5 g/L after the optimization of culture conditions. This study describes a novel producer of ST and TM and outlines the complete process undertaken for Streptomyces sp. strain fd1-xmd genome mining.

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Funding

This work was financially supported by grants from the National Key R&D Program of China (2016YFA0500600), the Basic Research Project of Science and Technology Commission of Shanghai Municipality (17JC1401800), and the Youth Talent Training Program of Zhejiang Academy of Agricultural Sciences (2017R19R08E01). This work was also supported by grant from the Natural Science Foundation for the Youth (31700007).

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Correspondence to Guoping Zhao or Xiaoming Ding.

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This article does not contain any studies with human participants performed by any of the authors.

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The authors declare that they have no conflict of interest.

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Yu, Y., Tang, B., Dai, R. et al. Identification of the streptothricin and tunicamycin biosynthetic gene clusters by genome mining in Streptomyces sp. strain fd1-xmd. Appl Microbiol Biotechnol 102, 2621–2633 (2018). https://doi.org/10.1007/s00253-018-8748-4

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  • DOI: https://doi.org/10.1007/s00253-018-8748-4

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