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Manipulation of Kynurenine Pathway for Enhanced Daptomycin Production in Streptomyces roseosporus

机译:操纵Kynurenine途径以增强玫瑰孢链霉菌中达托霉素的产生

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Daptomycin is a cyclic lipopeptide natural product produced by Stretptomyces roseosporus, displaying good bactericidal activity against a wide range of gram-positive pathogens. Daptomycin contains a 13 amino acid and kynurenine (Kyn) is essential for optimal activity of daptomycin. In this study, we characterized the Kyn pathway in S. roseosporus and investigated its role in supplying precursor for daptomycin biosynthesis. Two genes (dptJ and tdo) coding for tryptophan-2,3-dioxgenase existed in the chromosome. dptJ is located in the daptomycin biosynthetic gene cluster, while tdo is in other locus. Disruption of dptJ or tdo resulted in reduced yield by ~50%. The introduction of an additional copy of dptJ but not tdo led to enhanced production of daptomycin by 110%. Furthermore, disruption of kyn encoding kynur-eninase showed improved daptomycin productivity by 30%. Our results demonstrated that the enhancement of Kyn supply through metabolic engineering approach is an efficient way to increase daptomycin production.
机译:达托霉素是由玫瑰链霉菌产生的环状脂肽天然产物,对多种革兰氏阳性病原体表现出良好的杀菌活性。达托霉素含有13个氨基酸,犬尿氨酸(Kyn)对于达托霉素的最佳活性至关重要。在这项研究中,我们表征了玫瑰孢菌中的Kyn途径,并研究了其在提供达托霉素生物合成前体中的作用。染色体中存在两个编码色氨酸-2,3-二氧合酶的基因(dptJ和tdo)。 dptJ位于达托霉素生物合成基因簇中,而tdo在其他基因座中。 dptJ或tdo的破坏导致产量降低约50%。引入另一份dptJ而非tdo导致了达托霉素的产量提高了110%。此外,编码kynur-eninase的kyn的破坏显示达托霉素的生产率提高了30%。我们的结果表明,通过代谢工程方法增强Kyn的供应是增加达托霉素产量的有效途径。

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