Delineating citrinin biosynthesis: Ctn-ORF3 dioxygenase-mediated multi-step methyl oxidation precedes a reduction-mediated pyran ring cyclization.
Delineating citrinin biosynthesis: Ctn-ORF3 dioxygenase-mediated multi-step methyl oxidation precedes a reduction-mediated pyran ring cyclization.
复制标题
描述柑橘素生物合成：Ctn-ORF3 双加氧酶介导的多步甲基氧化先于还原介导的吡喃环环化。
DOI：
10.1016/j.bmcl.2015.12.001
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发表时间：
2016
影响因子：
2.7
通讯作者：
H. Kwon
中科院分区：
文献类型：
--
作者：
Bijinu Balakrishnan;Ramya Chandran;S. Park;H. Kwon
桔霉素(3)是一种聚酮类真菌毒素，由红曲霉、青霉菌和曲霉产生。是许多农产品中的一种常见污染物。CtPKS是一种具有C端还原结构域的非还原型迭代聚酮合成酶，用于生成3的聚酮骨架。Ctn-orf1orctn-orf3基因的失活导致苯甲醛类化合物6的积累，ctPKS/ctnB6在酵母中异位表达，证明ctPKS在CtnB的支持下生成6，提示CTN-ORF1/CTN-ORF3将6转化为3。Δctn-orf1突变体还产生了一种新的苯二醛衍生物10。当将6或10输入ΔctPKS突变体时，很容易检测到3，这证实了6和10都参与了3的生物合成。6在异位表达系统中的生物转化实验表明，ctn-orf3的表达有效地消耗了ctn-orf1，而不是ctn-orf1的表达。然而，6的代谢物(S)却无法鉴定。一个重组的CTN-ORF3酶被证明能将6转化为10和一个假想的羧基衍生物8，证实了CTN-ORF3氧化6的外环甲基部分。因此，CTN-ORF1被建议还原8和随后的非酶反应来完成3的生物合成。本研究描绘了3的生物合成路线，提出了生化机制，即参与产生天然的二氢吡喃二酚结构。
Citrinin (3) is a polyketide-derived mycotoxin, that is, produced by Monascus, Penicillium, and Aspergillus spp. and is a common contaminant in a number of agricultural products. ctPKS, a non-reducing type iterative polyketide synthase with a C-terminal reductive domain, is proposed to generate the polyketide backbone of3. The targeted gene inactivation ofctn-orf1orctn-orf3gene resulted in the accumulation of a benzaldehyde derivative6, and the ectopic expression ofctPKS/ctnBin yeast produced6, demonstrating that ctPKS generates6with the support of CtnB and suggesting that Ctn-ORF1/Ctn-ORF3 converts6into3. The Δctn-orf1mutant also produced a novel benzdialdehyde derivative10. When either6or10was fed into a ΔctPKSmutant,3was readily detected, which confirms that both6and10are involved in the biosynthesis of3. A bioconversion experiment of6in the ectopic expression system demonstrated thatctn-orf3expression, but notctn-orf1expression, efficiently consumed6. The resulting metabolite(s) of6could not be identified, however. A recombinant Ctn-ORF3 enzyme was demonstrated to convert6into10and a hypothetical carboxylic derivative8, which substantiates that Ctn-ORF3 oxidizes the exocyclic methyl moiety of6. Ctn-ORF1 is thus proposed to reduce8and the subsequent non-enzymatic reactions to complete the biosynthesis of3. The present study delineates the biosynthetic route of3, proposing the biochemical mechanism, that is, involved in producing the natural dihydropyranoquinone structure.
影响因子：
--
作者：
Zabala AO;Xu W;Chooi YH;Tang Y
通讯作者：
Tang Y
DOI：
10.1016/j.bbagen.2005.02.001
发表时间：
2005-05-25
影响因子：
3
作者：
Smiley, JA;Kundracik, M;Axhemi, AA
通讯作者：
Axhemi, AA
影响因子：
4.9
作者：
Fisch, Katja M.;Skellam, Elizabeth;Simpson, Thomas J.
通讯作者：
Simpson, Thomas J.