Small-molecule elicitation of microbial secondary metabolites.

Small-molecule elicitation of microbial secondary metabolites.
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DOI:
10.1111/j.1751-7915.2010.00196.x
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发表时间:
2011-07
影响因子:
5.7
通讯作者:
Pettit RK
Pettit RK
中科院分区:
工程技术2区
文献类型:
--
作者:
Pettit RK

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微生物天然产物仍然是药物先导发现的无与伦比的资源,但重新发现率很高。细菌和真菌测序研究表明,许多菌株的生物合成潜力远远大于发酵观察到的。刺激这种沉默(神秘)途径的表达将使我们能够最大限度地提高微生物的化学多样性。隐藏的代谢途径可以在实验室中使用分子或基于培养的方法进行访问。与基于培养的方法相关的靶向方法是应用小分子诱导子来特异性地影响次级代谢物基因簇的转录。随着新的次级代谢物lunalides A和B、氧脂素、枝色素F和G、nygerone A、毛球蛋白-542、-540和-510、sphaerolone、二氢sphaerolone、mutolide和pestalone的分离,以及已知次级代谢物如青霉素和杆菌肽的产量增加,化学诱导被证明是增加天然产物库的有效方式。
Microbial natural products continue to be an unparalleled resource for pharmaceutical lead discovery, but the rediscovery rate is high. Bacterial and fungal sequencing studies indicate that the biosynthetic potential of many strains is much greater than that observed by fermentation. Prodding the expression of such silent (cryptic) pathways will allow us to maximize the chemical diversity available from microorganisms. Cryptic metabolic pathways can be accessed in the laboratory using molecular or cultivation‐based approaches. A targeted approach related to cultivation‐based methods is the application of small‐molecule elicitors to specifically affect transcription of secondary metabolite gene clusters. With the isolation of the novel secondary metabolites lunalides A and B, oxylipins, cladochromes F and G, nygerone A, chaetoglobosin‐542, ‐540 and ‐510, sphaerolone, dihydrosphaerolone, mutolide and pestalone, and the enhanced production of known secondary metabolites like penicillin and bacitracin, chemical elicitation is proving to be an effective way to augment natural product libraries.
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