A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors,Angewandte Chemie International Edition

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A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-11-30 , DOI: 10.1002/anie.202015462
Haidong Peng _{1,

2} , Yaya Wang ₁ , Kai Jiang ₁ , Xinru Chen ₁ , Wenlu Zhang ₁ , Yanan Zhang ₁ , Zixin Deng _{1,

2} , Xudong Qu _{1,

2}

Affiliation

4‐Androstenedione (4‐AD) and progesterone (PG) are two of the most important precursors for synthesis of steroid drugs, however their current manufacturing processes suffer from low efficiency and severe environmental issues. In this study, we decipher a dual‐role reductase (mnOpccR) in the phytosterols catabolism, which engages in two different metabolic branches to produce the key intermediate 20‐hydroxymethyl pregn‐4‐ene‐3‐one (4‐HBC) through a 4‐e reduction of 3‐oxo‐4‐pregnene‐20‐carboxyl‐CoA (3‐OPC‐CoA) and 2‐e reduction of 3‐oxo‐4‐pregnene‐20‐carboxyl aldehyde (3‐OPA), respectively. Inactivation or overexpression of mnOpccR in the Mycobacterium neoaurum can achieve exclusive production of either 4‐AD or 4‐HBC from phytosterols. By utilizing a two‐step synthesis, 4‐HBC can be efficiently converted into PG in a scalable manner (100 gram scale). This study deciphers a pivotal biosynthetic mechanism of phytosterol catabolism and provides very efficient production routes of 4‐AD and PG.

中文翻译：

植物甾醇分解代谢的双重作用还原酶可有效生产有价值的类固醇前体

4-雄烯二酮（4-AD）和孕酮（PG）是合成类固醇药物的两个最重要的前体，但是它们目前的生产过程效率低下，环境问题严峻。在这项研究中，我们破译了植物甾醇分解代谢中的双重作用还原酶（mnOpccR），该酶参与两个不同的代谢分支，从而通过一个关键的中间体20-羟甲基pregn-4-ene-3-one（4-HBC）产生。分别减少3-氧代4-孕烯20-羧基CoA（3-OPC-CoA）和2-e减少3-氧代-4-孕烯20-羧基醛（3-OPA）。新生分枝杆菌中mnOpccR的失活或过表达可以从植物甾醇中独家生产4-AD或4-HBC。通过两步合成，可以以可扩展的方式（100克规模）将4-HBC有效地转化为PG。这项研究破译了植物甾醇分解代谢的关键生物合成机制，并提供了4-AD和PG的非常有效的生产途径。

更新日期：2020-11-30

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