Growth-Phase Sterigmatocystin Formation on Lactose Is Mediated via Low Specific Growth Rates in Aspergillus nidulans.

Growth-Phase Sterigmatocystin Formation on Lactose Is Mediated via Low Specific Growth Rates in Aspergillus nidulans.
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DOI:
10.3390/toxins8120354
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发表时间:
2016-11-28
期刊:
影响因子:
4.2
通讯作者:
Fekete E
Fekete E
中科院分区:
医学2区
文献类型:
--
作者:
Németh Z;Molnár ÁP;Fejes B;Novák L;Karaffa L;Keller NP;Fekete E

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曲霉产生的杂色曲霉素 (ST) 等聚酮化合物霉菌毒素的种子污染是一个世界性问题。 ST 生物合成途径在构巢曲霉中得到了很好的表征,但与碳源相关的监管方面仍然是个谜。对于乳糖来说尤其如此,因为一些 ST 生产突变株仍然在乳糖上合成 ST,但不在其他碳底物上合成 ST。在这里,动力学数据显示,对于 d-葡萄糖,ST 仅在培养基中的糖耗尽后形成,而对于乳糖,当大部分碳源仍然可用时,ST 才会出现。乳糖上的生物质特定 ST 产量显着高于 d-葡萄糖,这表明 ST 形成可能是由碳分解代谢物调节机制介导的,或者是由乳糖可达到的低比生长率诱导的。这些假设通过 d-葡萄糖限制的恒化器型连续发酵进行了测试。高生长速率时没有形成ST,而低生长速率则导致形成0.4 mg·L−1 ST。 CreA 突变株也获得了类似的结果。我们得出的结论是,低特定生长率可能是构巢曲霉乳糖生长中期 ST 形成的主要原因,并且碳利用率可能在生物合成过程中发挥一般调节作用。
Seed contamination with polyketide mycotoxins such as sterigmatocystin (ST) produced by Aspergilli is a worldwide issue. The ST biosynthetic pathway is well-characterized in A. nidulans, but regulatory aspects related to the carbon source are still enigmatic. This is particularly true for lactose, inasmuch as some ST production mutant strains still synthesize ST on lactose but not on other carbon substrates. Here, kinetic data revealed that on d-glucose, ST forms only after the sugar is depleted from the medium, while on lactose, ST appears when most of the carbon source is still available. Biomass-specified ST production on lactose was significantly higher than on d-glucose, suggesting that ST formation may either be mediated by a carbon catabolite regulatory mechanism, or induced by low specific growth rates attainable on lactose. These hypotheses were tested by d-glucose limited chemostat-type continuous fermentations. No ST formed at a high growth rate, while a low growth rate led to the formation of 0.4 mg·L−1 ST. Similar results were obtained with a CreA mutant strain. We concluded that low specific growth rates may be the primary cause of mid-growth ST formation on lactose in A. nidulans, and that carbon utilization rates likely play a general regulatory role during biosynthesis.
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