High-yield strain and construction method of cyclic lipopeptide antibiotics hemastatin

Abstract

The invention discloses a high-producing strain for the cyclic lipopeptide antibiotic--himastatin and a construction method thereof. The high-producing strain for himastatin is constructed by inactivating the hmtA gene or hmtB gene of S. himastatinicus sp.Nov, so the high-producing mutant strain S. himastatinicus sp.Nov for himastatin is obtained, wherein the nucleotide sequence of the hmtA gene is as shown in SEQ ID No. 1 and the nucleotide sequence of the hmtB gene is as shown in SEQ ID No. 3. According to the invention, the hmtA-inactivated mutant strain S. himastatinicus sp.Nov Ju2014 and the hmtB-inactivated mutant strain S. himastatinicus sp.Nov Ju2015 are respectively obtained by inactivating the Mer-family transcriptional regulation gene hmtA and the acetyl glutamic acid kinase gene hmtB at the upper stream of the biosynthesis gene cluster of the cyclic lipopeptide antibiotic--himastatin of S. himastatinicus sp.Nov. The himastatin output of the mutant strain S. himastatinicus sp.Nov Ju2014 and the mutant strain S. himastatinicus sp.Nov Ju2015 is more than 10 times that of a wild strain S. himastatinicus sp.Nov. Thus, successful construction of the two high-producing mutant strains for the cyclic lipopeptide antibiotic--himastatin enables acceleration of the industrialization process of himastatin to be possible and hopeful.

Description

Technical field: [0001] The invention belongs to the field of microbial genetic engineering and metabolic engineering, and in particular relates to a high-yield strain of cyclic lipopeptide antibiotic himastatin and a construction method thereof. Background technique: [0002] Cyclic peptide compounds are a class of cyclic compounds formed by amide bonds, and are mainly complex molecules composed of amino acids, glycopeptides, lipopeptides and nucleoside peptides after a series of modifications. Such compounds are widely found in invertebrates (sponges, sea squirts, bryozoans, etc.), bacteria, cyanobacteria, fungi, and actinomycetes, and most of them have complex and novel structural features, the most prominent features of which are ring structures and Various amino acid derivative building blocks. The ring structure endows the compounds with certain physical rigidity and resistance to proteolysis, and different derivative structures make the compounds have various physiol...

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Problems solved by technology

[0003] However, some of these cyclic peptide compounds have been withdrawn from clinical trials due to their poor water solubility, large side effects, or low yields of compounds, which also indirectly explains the structural modification and optimization of these compounds or the improvement of their yields. the necessity and urgency of

Moreover, because most of these compounds have complex structures, numerous chiral centers and the selection of ring-closing positions seriously restrict the efficiency or industrialization process of structural modification of such compounds.

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