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在化学诱导下使用平行稳定同位素标签对自然产品生产的变化进行表征

Liana Zaroubi¹, Bruno S Paulo^2,3, Ethan Fung¹

¹Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.

ACS chemical biology

|September 17, 2025

概括

研究人员使用化学诱导剂来刺激休眠的微生物基因,发现了新化合物,如二胺A和B. 这种方法采用稳定同位素标记,揭示了不同的条件如何影响天然产品生物合成.

科学领域:

微生物学微生物学
自然产品化学自然产品化学
代谢学代谢学代谢学

背景情况:

微生物拥有众多的生物合成基因集群 (BGCs),但在实验室培养中产生有限的二次代谢产物.
化学诱导剂可以通过一株多化合物 (OSMAC) 策略诱导二次代谢产物.
在诱导下表征代谢变异需要超越传统方法的先进分析工具.

研究的目的:

在各种OSMAC条件下,研究*Paraburkholderia*菌株的二次代谢物产生.
评估化学诱导物对微生物代谢物的影响,并确定新型化合物.
评估IsoAnalyst用于表征二次代谢变异的实用性.

主要方法:

应用一株多化合物 (OSMAC) 策略与化学诱导物.
使用IsoAnalyst,一种稳定的同位素标记技术,来跟踪代谢物生物合成.
采用多维NMR和总合成来阐明结构和确定绝对配置.

主要成果:

在不同的OSMAC条件下对三种*Paraburkholderia*菌株进行分析,发现了二次代谢的显著变化.
IsoAnalyst成功地分化了代谢物,并将它们与BGCs联系起来.
抗生素rifaximin强烈诱导了一种特定的化合物类,导致发现了putrescinamides A和B.

结论:

稳定同位素标记实验提供了系统范围内的二次代谢物生物合成的洞察力.
诱导体选择显著影响 *Burkholderiales* 菌株中的代谢物诱导.
该研究强调了OSMAC和IsoAnalyst在发现新型天然产品方面的潜力.

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