Extending the Structural Diversity of Labdane Diterpenoids from Marine-Derived Fungus Talaromyces sp. HDN151403 Using Heterologous Expression.
Extending the Structural Diversity of Labdane Diterpenoids from Marine-Derived Fungus Talaromyces sp. HDN151403 Using Heterologous Expression.
复制标题
扩大海洋真菌Talarmyces sp.Labdane二萜类化合物的结构多样性HDN151403采用外源表达。
作者：
杂环生物合成已成为激活真菌沉默生物合成基因簇（BGC）和高效利用真菌遗传资源的有效手段。本文中，通过在构巢曲霉中异源表达沉默BGC（labd），发现了13种拉布拉多二萜衍生物，包括5种未描述的命名为talarobicins A-E（3-7）的二萜衍生物。利用广泛的MS和NMR光谱方法，以及电子圆二色谱（ECD）计算，它们的结构与绝对构型进行了阐明。其中talarobicin B（4）是第一个3，18-dinor-2，3：4，18-diseco-labdane二萜，其A环C2-C3键断裂，C-3和C-18位脱羧。塔拉比星B（4）代表青霉菌素和化合物13生物合成中的关键中间体。组合异源表达和饲养实验表明，细胞色素P450酶LabdC，LabdE和LabdF负责催化各种化学反应，如氧化，脱羧和甲基化。所有化合物均无细胞毒性，化合物2和8对耐甲氧西林凝固酶阴性葡萄球菌（MRCNS）和蜡状芽孢杆菌显示出抑制作用。
Heterologous biosynthesis has become an effective means to activate fungal silent biosynthetic gene clusters (BGCs) and efficiently utilize fungal genetic resources. Herein, thirteen labdane diterpene derivatives, including five undescribed ones named talarobicins A–E (3–7), were discovered via heterologous expression of a silent BGC (labd) in Aspergillus nidulans. Their structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as electronic circular dichroism (ECD) calculations. These labdanes belong to four skeleton types, and talarobicin B (4) is the first 3,18-dinor-2,3:4,18-diseco-labdane diterpene with the cleavage of the C2–C3 bond in ring A and the decarboxylation at C-3 and C-18. Talarobicin B (4) represents the key intermediate in the biosynthesis of penioxalicin and compound 13. The combinatorial heterologous expression and feeding experiments revealed that the cytochrome P450 enzymes LabdC, LabdE, and LabdF were responsible for catalyzing various chemical reactions, such as oxidation, decarboxylation, and methylation. All of the compounds are noncytotoxic, and compounds 2 and 8 displayed inhibitory effects against methicillin-resistant coagulase-negative staphylococci (MRCNS) and Bacillus cereus.
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影响因子：
5.1
作者：
Chiang, Yi-Ming;Wang, Clay C. C.;Lin, Tzu-Shyang
通讯作者：
Lin, Tzu-Shyang
影响因子：
14.9
作者：
Grigoriev IV;Nikitin R;Haridas S;Kuo A;Ohm R;Otillar R;Riley R;Salamov A;Zhao X;Korzeniewski F;Smirnova T;Nordberg H;Dubchak I;Shabalov I
通讯作者：
Shabalov I
影响因子：
2.2
作者：
Qi, Bowen;Jia, Fangfang;Shi, She-Po
通讯作者：
Shi, She-Po
DOI：
10.1093/bioadv/vbab016
发表时间：
2021
期刊：
Bioinformatics advances
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.1
作者：
BRAUN, S;BREITENBACH, H
通讯作者：
BREITENBACH, H