Medium-chain fatty acids affect citrinin production in the filamentous fungus Monascus ruber
Medium-chain fatty acids affect citrinin production in the filamentous fungus Monascus ruber
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DOI：
10.1128/aem.66.3.1120-1125.2000
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发表时间：
2000-03-01
影响因子：
4.4
通讯作者：
François, J
中科院分区：
文献类型：
--
作者：
Hajjaj, H;Klaébé, A;François, J
在葡萄糖和谷氨酸存在下的浸没培养期间，丝状真菌红曲霉产生水溶性红色素以及桔霉素，桔霉素是一种对动物具有肾毒性和肝毒性作用的真菌毒素。通过C-13核磁共振对来自用[1-C-13]-、[2-C-13]-或[1，2-C-13]乙酸盐培养的菌丝体的C-13-色素分子的分析表明，红色素的生物合成既使用聚酮途径来产生发色团结构，又使用脂肪酸合成途径，以产生中链脂肪酸（辛酸），然后通过酯交换反应将其结合到发色团上。因此，为了提高色素产量，我们试图通过将中链脂肪酸添加到培养液中来缩短中链脂肪酸的从头合成。在碳链范围为6至18个碳原子的脂肪酸中，只有辛酸显示出30至50%的红色素产生刺激，其机制与预期相反，不涉及其在发色团骨架上的直接酯交换。然而，测试的中链和长链脂肪酸很容易被真菌同化，并且在8至12个碳原子的脂肪酸的情况下，其初始量的30至40%以相应的甲基酮1个碳单位短的形式瞬时积累在生长培养基中。非常有趣的是，当这些脂肪酸或其相应的甲基酮被添加到培养基中时，它们引起红曲霉桔霉素产生的强烈减少，甚至完全抑制。一些数据表明，这种影响可能是由于新合成的桔霉素（或桔霉素途径中的中间体）的降解，由中链脂肪酸或甲基酮诱导的过氧化物酶体增殖产生的过氧化氢。
During submerged culture in the presence of glucose and glutamate, the filamentous fungus Monascus ruber produces water-soluble red pigments together with citrinin, a mycotoxin with nephrotoxic and hepatoxic effects on animals. Analysis of the C-13-pigment molecules from mycelia cultivated with [1-C-13]-, [2-C-13]-, or [1,2-C-13]acetate by C-13 nuclear magnetic resonance indicated that the biosynthesis of the red pigments used both the polyketide pathway, to generate the chromophore structure, and the fatty acid synthesis pathway, to produce a medium-chain fatty acid (octanoic acid) which was then bound to the chromophore by a transesterification reaction. Hence, to enhance pigment production, we tried to short-circuit the de novo synthesis of medium-chain fatty acids by adding them to the culture broth. Of fatty acids with carbon chains ranging from 6 to 18 carbon atoms, only octanoic acid showed a 30 to 50% stimulation of red pigment production, by a mechanism which, in contrast to expectation, did not involve its direct trans-esterification on the chromophore backbone. However, the medium- and long-chain fatty acids tested were readily assimilated by the fungus, and in the case of fatty acids ranging from 8 to 12 carbon atoms, 30 to 40% of their initial amount transiently accumulated in the growth medium in the form of the corresponding methylketone 1 carbon unit shorter. Very interestingly, these fatty acids or their corresponding methylketones caused a strong reduction in, or even a complete inhibition of, citrinin production by M, ruber when they were added to the medium. Several data indicated that this effect could be due to the degradation of the newly synthesized citrinin (or an intermediate in the citrinin pathway) by hydrogen peroxide resulting from peroxisome proliferation induced by medium-chain fatty acids or methylketones.