Heterologous expression of lantibiotic lexapeptide biosynthetic gene cluster homologue
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Abstract:
Lantibiotics attract extensive attention in the field of discovery and development of antibiotics due to its special action mode and barely observed drug-resistant mutation after being applied for decades. Lexapeptide is a type V lantibiotic recently uncovered via a functional genome mining approach (LEXAS) and has strong antibacterial activity against Gram positive bacteria including MRSA and MRSE. A gene cluster (lxm2) similar to the lexapeptide biosynthetic gene cluster was identified through screening the Streptomyces galtieri genomic DNA bacterial artificial chromosome (BAC) library via LEXAS. The BAC clone carrying lxm2 was introduced into Streptomyces lividians for heterologous expression,leading to the production of lexapeptide and a novel peak in HPLC. The production of lexapeptide and the new peak was disappeared when the lxm2 gene cluster was removed from the BAC clone. Based on NMR spectrometry and high resolution mass spectrometry,the structure of the new compound was identified to be a highly modified linear hexapeptide with sequence identical to the N-terminal six amino acids of lexapeptide,thus Lxm-N-hexapeptide was given as its name. The Lxm-N-hexapeptide did not exhibit antibacterial activity.
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徐利军,王业民,徐敏,赵志龙,高贵喜,陶美凤. Heterologous expression of lantibiotic lexapeptide biosynthetic gene cluster homologue[J]. Jorunal of Huazhong Agricultural University,2020,39(5):93-100.