Harnessing the Substrate Promiscuity of Dioxygenase AsqJ and Developing Efficient Chemoenzymatic Synthesis for Quinolones.
Harnessing the Substrate Promiscuity of Dioxygenase AsqJ and Developing Efficient Chemoenzymatic Synthesis for Quinolones.
复制标题
利用二氧酶ASQJ的底物滥交，并为喹诺酮类酮开发有效的化学酶合成。
DOI：
10.1021/acscatal.1c01150
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发表时间：
2021-06-18
期刊：
影响因子：
12.9
通讯作者：
Chang, Wei-chen
中科院分区：
文献类型：
--
作者：
Tang, Haoyu;Tang, Yijie;Kurnikov, Igor, V;Liao, Hsuan-Jen;Chan, Nei-Li;Kurnikova, Maria G.;Guo, Yisong;Chang, Wei-chen
自然界已经在天然产物生物合成途径中开发了复杂性生成反应。然而，直接利用这些途径来制备化合物文库仍然具有挑战性，这是由于有限的底物范围、涉及多步反应以及这些复杂的酶促转化的适度稳健性。另一方面，合成化学提供了制备天然产物类似物的替代方法。然而，由于目标分子上附加的复杂和多样的官能团，通常需要专门的设计和开发合成策略。在此，通过利用化学-酶促合成的力量，我们报告了一种方法，以弥合生物和合成策略之间的差距差距，在喹诺酮类生物碱类似物的制备。通过计算机模拟分析，化学合成了预测的底物类似物。这些底物类似物的AsqJ催化的不对称环氧化之后，通过刘易斯酸引发的环收缩来完成葡萄黄素的形成。我们评估了该方法在克级反应中的稳健性。最后，通过化学酶级联，有效地制备了喹诺酮类生物碱库。
Nature has developed complexity–generating reactions within natural product biosynthetic pathways. However, direct utilization of these pathways to prepare compound libraries remains challenging due to limited substrate scopes, involvement of multiple-step reactions, and moderate robustness of these sophisticated enzymatic transformations. Synthetic chemistry, on the other hand, offers an alternative approach to prepare natural product analogs. However, owing to complex and diverse functional groups appended on the targeted molecules, dedicated design and development of synthetic strategies are typically required. Herein, by leveraging the power of chemo-enzymatic synthesis, we report an approach to bridge the gap between biological and synthetic strategies in the preparation of quinolone alkaloid analogs. Leading by in silico analysis, the predicted substrate analogs were chemically synthesized. The AsqJ-catalyzed asymmetric epoxidation of these substrate analogues was followed by an Lewis Acid-triggered ring contraction to complete the viridicatin formation. We evaluated the robustness of this method in gram-scale reactions. Lastly, through chemoenzymatic cascades, a library of quinolone alkaloids is effectively prepared.
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影响因子：
15
作者：
Dunham NP;Chang WC;Mitchell AJ;Martinie RJ;Zhang B;Bergman JA;Rajakovich LJ;Wang B;Silakov A;Krebs C;Boal AK;Bollinger JM Jr
通讯作者：
Bollinger JM Jr
影响因子：
16.6
作者：
Kishimoto S;Hara K;Hashimoto H;Hirayama Y;Champagne PA;Houk KN;Tang Y;Watanabe K
通讯作者：
Watanabe K
影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
DOI：
10.1002/anie.202017086
发表时间：
2021-04-06
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Einsiedler M;Jamieson CS;Maskeri MA;Houk KN;Gulder TAM
通讯作者：
Gulder TAM
DOI：
10.1073/pnas.0909649106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Matthews, Megan L.;Neumann, Christopher S.;Bollinger, J. Martin, Jr.
通讯作者：
Bollinger, J. Martin, Jr.