| Summary: | <p>Abstract</p> <p>Background</p> <p>Nikkomycins are a group of peptidyl nucleoside antibiotics produced by <it>Streptomyces ansochromogenes</it>. They are competitive inhibitors of chitin synthase and show potent fungicidal, insecticidal, and acaricidal activities. Nikkomycin X and Z are the main components produced by <it>S. ansochromogenes</it>. Generation of a high-producing strain is crucial to scale up nikkomycins production for further clinical trials.</p> <p>Results</p> <p>To increase the yields of nikkomycins, an additional copy of nikkomycin biosynthetic gene cluster (35 kb) was introduced into nikkomycin producing strain, <it>S. ansochromogenes </it>7100. The gene cluster was first reassembled into an integrative plasmid by Red/ET technology combining with classic cloning methods and then the resulting plasmid(pNIK)was introduced into <it>S. ansochromogenes </it>by conjugal transfer. Introduction of pNIK led to enhanced production of nikkomycins (880 mg L<sup>-1</sup>, 4 -fold nikkomycin X and 210 mg L<sup>-1</sup>, 1.8-fold nikkomycin Z) in the resulting exconjugants comparing with the parent strain (220 mg L<sup>-1 </sup>nikkomycin X and 120 mg L<sup>-1 </sup>nikkomycin Z). The exconjugants are genetically stable in the absence of antibiotic resistance selection pressure.</p> <p>Conclusion</p> <p>A high nikkomycins producing strain (1100 mg L<sup>-1 </sup>nikkomycins) was obtained by introduction of an extra nikkomycin biosynthetic gene cluster into the genome of <it>S. ansochromogenes</it>. The strategies presented here could be applicable to other bacteria to improve the yields of secondary metabolites.</p>
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