Biotechnology Bulletin ›› 2017, Vol. 33 ›› Issue (9): 145-152.doi: 10.13560/j.cnki.biotech.bull.1985.2017-0276

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Mining the Cryptic Bioactive Secondary Metabolites from Streptomyces vietnamensis Using a‘Tree-Removal’Strategy

LIN Hai-zhou1,2,3 CHEN Zhou-qin2 WANG Yan4 GUO Jun2 ZHU Hong-hui2 DENG Ming-rong2   

  1. 1. South China Sea Institute of Oceanology,the Chinese Academy of Sciences,Guangzhou 510301；
    2. State Key Laboratory of Applied Microbiology Southern China,Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application,Guangdong Open Laboratory of Applied Microbiology,Guangdong Institute of Microbiology,Guangzhou 510070；
    3. University of Chinese Academy of Sciences,Beijing 100049；
    4. Guangdong Science and Technology Library,Guangzhou 510070
  • Received:2017-04-07 Online:2017-09-01 Published:2017-09-15

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Abstract:

This study aims to discover novel bioactive substances by activating the cryptic biosynthetic gene clusters of secondary metabolites from Streptomyces vietnamensis with appropriate strategies. The study was carried out in a S. vietnamensis mutant DMR1. In this mutant,the key biosynthetic genes,gra-orf1-3,of the dominant product were knocked out,resulting in deficiency in granaticin production. The strain was subject to nutrient condition changing,inducer adding and heat shocking. The antimicrobial activities of the fermentation crude extracts were tested using agarose diffusion method and TLC-bioautography. Results showed that the fermentation crude extracts of Gause No.1 and ISP3 presented significant inhibitory effects against Bacillus subtilis ATCC6633,Staphylococcus aureus ATCC6538 as well as multidrug resistant Staphylococcus aureus strains ATCC43300 and 206. With adding 3% DMSO to the media,not only did the activities of the fermentation crude extracts of Gause No.1 and ISP3 against the afore said strains increase,but also the spectrum broadened into against Escherichia coli ATCC8739,Candida albicans ATCC10231 and multidrug resistant E. coli and Salmonella sp. strains. The newly discovered bioactive substances from S. vietnamensis showed extensive activities against both gram-positive and gram-negative bacteria as well as yeast. More importantly,some of the crude extracts were significantly active against all the tested drug-resistant strains. These results indicate a possibility of a novel type of antibiotic. The results presented in this paper illustrate that the so-called ‘tree-removal’ strategy can improve the mining efficiency of the cryptic bioactive secondary metabolites.

Key words: cryptic secondary metabolites, ‘tree-removal&rsquo, strategy, activation, multidrug resistant bacterium, Streptomyces vietnamensis