Resistant Mutant Screening of Pleuromutilin High-producing Clitopilus prunulus

doi:Q819

China Biotechnology

2010, Vol. 30

Issue (08): 67-71 DOI: Q819

Resistant Mutant Screening of Pleuromutilin High-producing Clitopilus prunulus

CHEN Xiao-li,ZHANG Wen-qi,HU Chang-hua

Institute of Modern Biopharmaceuticals, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716,China

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Abstract

Pleuromutilin is one of the tricyclic structural diterpenoid antibiotics, and is currently being used as an intermediate for semisynthetic antibiotics such as veterinary antibiotics tiamulin, valnemulin, and human-used antibiotic retapamulin. These compounds inhibit bacterial protein synthesis by specifically targeting the large subunit (50S) of the bacterial ribosome and exhibit excellent in vitro and in vivo antibacterial activity against gram-positive pathogens . Recently, a series of novel water-soluble pleuromutilin derivatives bearing a purine ring have been developed. These developing pleuromutilin derivatives stimulate the need of pleuromutilin from Clitopilus prunulus. But the strain improvement about Clitopilus prunulus has not been reported. A large number of pleuromutilin high-producing strains were obtained from the original basidiomycetes strain Clitopilus prunulus after nitrosoguanidine mutagenesis and following continuous subculture in the broth with nystatin, terbinafine, sodium dodecyl benzene sulfonate, and lauryl trimethyl ammonium chloride respectively. Mutants with antibiotic resistance which antibiotics targeted on ergosterol biosynthesis pathway, got a higher forward mutation rate. The pleuromutilin yield of mutant strain pn163, a nystatin resistant mutant with genetic stability, was increased by 38.50% while ergosterol was decreased to 29.29%, which was supposed to correlate with cell membrane permeability.

Key words： Pleuromutilin Basidiomycetes Resistant screening Strain improvement Ergosterol

Received: 22 February 2010 Published: 25 August 2010

Corresponding Authors: Hu Chang-hua E-mail: chhhu@vip.sina.com

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CHEN Xiao-Li, ZHANG Wen-Qi, HU Chang-Hua. Resistant Mutant Screening of Pleuromutilin High-producing Clitopilus prunulus. China Biotechnology, 2010, 30(08): 67-71.

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https://manu60.magtech.com.cn/biotech/Q819 OR https://manu60.magtech.com.cn/biotech/Y2010/V30/I08/67

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