Biotechnology Bulletin ›› 2017, Vol. 33 ›› Issue (9): 235-243.doi: 10.13560/j.cnki.biotech.bull.1985.2017-0275

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Characterization of Clavulanic Acid High-yield Streptomyces clavuligerus Industrial Strain by Transcriptome Analysis

QIN Rong-huo1,2,FU Jia-fang2,ZONG Gong-li2,WANG Zhi-yu2,CAO Guang-xiang1,2   

  1. 1. School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Ji’nan 250022;
    2. Shandong Medicinal Biotechnology Center,Ji’nan 250062
  • Received:2017-04-07 Online:2017-09-01 Published:2017-09-15

Abstract: This work aims to explore the molecular mechanism of clavulanic acid(CA)high-yield Streptomyces clavuligerus industrial strain. Transcriptome high-throughput sequencing was performed to compare the differential gene expressions between standard strain ATCC27064 and high-yield industrial strain F613-1,and comprehensive analysis was carried out combined with the phenotypic differences between them. The phenotypic results showed that F613-1 grew differently in growth rate,aerial mycelium morphology and spore formation in solid medium,compared with the standard strain. In the liquid culture,the growth rate of the two strains demonstrated no difference,but the sugar consumption of F613-1 significantly decreased,and the CA yield was 11.7 times higher than that of ATCC27064.Transcriptome analysis indicated that the expressions of both CA cluster genes and pathway-specific regulatory genes significantly increased;while the expressions of holomycin(CA by-product)cluster genes significantly decreased. On the other hand,the transcriptional levels of genes associated with arginine and glyceradldehyde-3P(raw materials for CA synthesis)metabolic pathways changed significantly,i.e.,up-regulated for arginine and down-regulated for glyceradldehyde-3P. Besides,the expressions of over80 genes involved in ABC transport system obviously changed,and 42 remarkably up-regulated and 38 down-regulated. The main reason of F613-1 highly produces clavulanic acid possibly lies in the increased transcription of CA cluster genes and relative regulatory genes,the silence of cluster genes involved in CA by-products,and the accumulation of arginine and alyceradldehyde-3P.

Key words: Streptomyces clavuligerus, industrial strain, transcriptome, clavulanic acid