Media studies to enhance the production of verticillins facilitated by in situ chemical analysis.

Media studies to enhance the production of verticillins facilitated by in situ chemical analysis.
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DOI:
10.1007/s10295-018-2083-8
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发表时间:
2018-12
影响因子:
3.4
通讯作者:
Oberlies NH
Oberlies NH
中科院分区:
工程技术3区
文献类型:
--
作者:
Amrine CSM;Raja HA;Darveaux BA;Pearce CJ;Oberlies NH

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Verticillins是一组表聚硫代二氧代哌嗪生物碱,具有很强的细胞毒性。为了进一步评估它们的潜力,需要更多的这些化合物用于体内研究和通过半合成的类似物开发。为了优化这些次级代谢产物的生物合成,在一系列发酵条件下在两种不同的真菌菌株(MSX 59553和MSX 79542)中分析了它们的产生。这些研究通过使用液滴-液体微连接表面取样探针(液滴探针)来促进,该探针使得能够直接从培养物的表面原位进行化学分析。这些实验表明,轮枝菌素的生产受到生长条件的极大影响;当真菌菌株在燕麦粉基培养基上生长时,注意到这些生物碱的量显著较高。使用这些技术在测试的生长条件中选择最佳,提高了轮枝青霉素类似物的产量,同时将发酵所需的时间从5周减少到约11天。重要的是,我们以前可以每6周供应5-10毫克,现在我们能够通过实验室规模发酵每月供应50-150毫克的关键类似物。本文的在线版本(10.1007/s10295-018-2083-8)包含补充材料,可供授权用户使用。
Verticillins are a group of epipolythiodioxopiperazine alkaloids that have displayed potent cytotoxicity. To evaluate their potential further, a larger supply of these compounds was needed for both in vivo studies and analogue development via semisynthesis. To optimize the biosynthesis of these secondary metabolites, their production was analyzed in two different fungal strains (MSX59553 and MSX79542) under a suite of fermentation conditions. These studies were facilitated by the use of the droplet-liquid microjunction-surface sampling probe (droplet probe), which enables chemical analysis in situ directly from the surface of the cultures. These experiments showed that the production of verticillins was greatly affected by growth conditions; a significantly higher quantity of these alkaloids was noted when the fungal strains were grown on an oatmeal-based medium. Using these technologies to select the best among the tested growth conditions, the production of the verticillin analogues was increased while concomitantly decreasing the time required for fermentations from 5 weeks to about 11 days. Importantly, where we could previously supply 5–10 mg every 6 weeks, we are now able to supply 50–150 mg quantities of key analogues per month via laboratory scale fermentation. The online version of this article (10.1007/s10295-018-2083-8) contains supplementary material, which is available to authorized users.
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