biostudies-literatureLi JNatural Science Foundation of Guangxi ProvinceNational Natural Science Foundation of China792023https://www.ebi.ac.uk/biostudies/studies/S-EPMC8823705biostudies-literatureUnknown92,3,5,6-Tetramethylpyrazine (TMP) is an active pharmaceutical ingredient originally isolated from <i>Ligusticum wallichii</i> for curing cardiovascular and cerebrovascular diseases and is widely used as a popular flavoring additive in the food industry. Hence, there is a great interest in developing new strategies to produce this high-value compound in an ecological and economical way. Herein, a cost-competitive combinational approach was proposed to accomplish green and high-efficiency production of TMP. First, microbial cell factories were constructed to produce acetoin (3-hydroxy-2-butanone, AC), an endogenous precursor of TMP, by introducing a biosynthesis pathway coupled with an intracellular NAD⁺ regeneration system to the wild-type <i>Escherichia coli</i>. To further imprFrontiers in bioengineering and biotechnologyA Green Route for High-Yield Production of Tetramethylpyrazine From Non-Food Raw Materials.PMC88237052018GXNSFBA28101721868007 21466007Li JLu JMa ZChen XXie NDiao MfalseA Green Route for High-Yield Production of Tetramethylpyrazine From Non-Food Raw Materials.2,3,5,6-Tetramethylpyrazine (TMP) is an active pharmaceutical ingredient originally isolated from <i>Ligusticum wallichii</i> for curing cardiovascular and cerebrovascular diseases and is widely used as a popular flavoring additive in the food industry. Hence, there is a great interest in developing new strategies to produce this high-value compound in an ecological and economical way. Herein, a cost-competitive combinational approach was proposed to accomplish green and high-efficiency production of TMP. First, microbial cell factories were constructed to produce acetoin (3-hydroxy-2-butanone, AC), an endogenous precursor of TMP, by introducing a biosynthesis pathway coupled with an intracellular NAD⁺ regeneration system to the wild-type <i>Escherichia coli</i>. To further impr2021-01-01T00:00:00Z20212025-04-19T10:47:07.769Z2025-04-19T10:47:07.769ZS-EPMC88237053514596110.3389/fbioe.2021.792023