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Biotechnology Advances
Volume 55, 2022, 107904

Recent advances in microbial production of high-value compounds in the tetrapyrrole biosynthesis pathway

Jian Zhanga, Zhiyong Cuia, Yuan Zhua, Ziwei Zhua, Qingsheng Qia,b

National Glycoengineering Research Center, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, PR China.


Tetrapyrroles are essential metabolic components produced by almost all organisms, and they participate in various fundamental biological processes. Tetrapyrroles are used as pharmaceuticals, food additives, and nutraceuticals, as well as in agricultural applications. However, their production is limited by their low extraction yields from natural resources and by the complex reaction steps involved in their chemical synthesis. Through advances in metabolic engineering and synthetic biology strategies, microbial cell factories were developed as an alternative method for tetrapyrrole production. Herein, we review recent developments in metabolic engineering and synthetic biology strategies that promote the microbial production of high-value compounds in the tetrapyrrole biosynthesis pathway (e.g., 5-aminolevulinic acid, heme, bilins, chlorophyll, and vitamin B12). Furthermore, outstanding challenges to the microbial production of tetrapyrrole compounds, as well as their possible solutions, are discussed.

Keywords: Tetrapyrroles, 5-aminolevulinic acid, Heme, Chlorophyll, Vitamin B12, Microbial cell factory.

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