模块化聚基化合成酶的特征设计用于制造Pentaene类型的安二乙烯类似物
Yuhao Song1, Mark Hogan1, Jimmy Muldoon2
1School of Biomolecular and Biomedical Science, University College Dublin, D04 V1W8 Dublin, Ireland.
Molecules (Basel, Switzerland)
|March 28, 2024
概括
研究人员对Streptomyces nodosus进行了基因改造,以创建新型的丁烯类型的B. amphotericin. 这些新的化合物,虽然不是糖化或抗真菌,但提供了对聚烯宏化物生物合成的见解,以及未来抗生素开发的潜力.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 合成生物学 合成生物学
背景情况:
- 糖化聚烯宏化物是由actinomycetes产生的至关重要的抗真菌剂.
- 开发新型聚烯可能会导致改善抗生素疗法.
- 菌株Streptomyces nodosus是安福特二B的关键生产者,它是一种七烯聚烯宏化物.
研究的目的:
- 将Streptomyces nodosus基因重新编程,用于合成安福特素B的五类似物.
- 调查烯作为替代基质的实用性,用于研究晚期生物合成修饰.
- 为了生成和表征具有修改的聚基合成酶模块的新型五烯化合物.
主要方法:
- 通过删除特定的多基胺合成酶模块 (5和6) 来对Streptomyces nodosus进行基因工程.
- 一个链终结类化酶与模块16的融合,以产生菌株M57-16TE.
- 用混合模块替换15号,16号和17号模块,以产生菌株M57-1517.
- 在工程菌株中分析五烯产量,结构和糖化状态.
主要成果:
- 改造后的菌株M57-16TE和M57-1517产生了减少的五烯产量.
- 菌株M57-1517产生了预测的全长五烯麦克罗拉克的少量.
- 产生的主要五是从模块10,11,12中释放的中间体,表明较长链的不稳定性.
- 新型五烯没有糖化,也没有对Candida albicans表现出抗真菌活性.
结论:
- 对Streptomyces nodosus的基因操纵可以产生新的,非糖化五烯宏化物.
- 产生的五烯不是直接的抗真菌,但作为研究聚烯生物合成的有价值的工具.
- 进一步的随机突变发生和对这些菌株的查可能会确定新的抗真菌生产者.
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