Indirubin (IND), a bisindole alkaloid with remarkable pharmacological activities, has attracted significant attention in the pharmaceutical field due to its antileukemic, anti-inflammatory, and immunomodulatory properties. Currently, indirubin primarily relies on plant extraction and chemical synthesis, which are hindered by complex processes, low yields, and poor environmental compatibility. These challenges pose serious obstacles to clinical supply and sustainable industrial development. In recent years, microbial synthesis technology, which is based on synthetic biology and metabolic engineering, has provided a novel approach for the efficient production of indirubin. This method offers several advantages, including high efficiency, environmental sustainability, and eco-friendliness. Hence, this manuscript systematically summarizes the biosynthesis mechanisms of indirubin, the catalytic characteristics of key enzymes, the construction strategies of engineered bacteria, and the progress in fermentation condition. To address challenges such as the difficult separation of indirubin isomers, by-product inhibition, and industrialization bottlenecks, potential solutions are proposed, aiming to promote the green biomanufacturing of indirubin.
关键词:
生物合成;双加氧酶系统;大肠杆菌;发酵条件;单加氧酶系统;微生物代谢工程;生物合成机制;青黛
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This work was financially supported by the General Program of the National Natural Science Foundation of China, China (No. 82173976), the National Key Research and Development Program of China, China (No. 2018YFC1707205) and the College Students’Innovation and Entrepreneurship Training Program (No.S202410633063).
Keqian Li a,, Fangyu Xiang a,, Xin Yang a, Mengqi Liu a, Rui Long a, Li Han a, Ming Yang b, Dingku a, c,?, Yanan He a,?. Advances in microbial biosynthesis of indirubin[J]. Chinese Herbal Medicines (CHM),2026,18(1):45-58