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[Objective] L-histidine is a high-value, imidazole-containing amino acid with broad applications in the pharmaceutical, food, and additive industries. The fermentative production of L-histidine remains constrained by the low carbon flux through the core biosynthetic route, limited precursor availability, and by-product accumulation. [Methods] With Escherichia coli as the chassis, L-histidine biosynthesis was systematically improved through rational metabolic engineering. [Results] The flux toward L-histidine was enhanced by elimination of transcriptional attenuation of the histidine operon, introduction of an efficient adenosine triphosphate (ATP) phosphoribosyltransferase mutant, and plasmid-based overexpression of key pathway genes. The pentose phosphate pathway was reconstructed to increase the precursor 5-phosphoribosyl pyrophosphate (PRPP) supply. In parallel, carbon loss was reduced by blocking formate- and acetate-forming pathways. Nitrogen sources were subsequently evaluated, and fermentation parameters, including temperature, pH, and dissolved oxygen, were systematically optimized. Under the optimized conditions, the L-histidine titer, yield, and productivity reached 34.84 g/L, 0.13 g/g, and 0.73 g/(L·h), respectively. In addition, the analysis of key gene expression and intracellular metabolites suggested that process optimization was conducive to enhancing the expression of the main synthetic pathway, improving energy and redox states, and increasing the ammonia donor supply. [Conclusion] The results establish an effective metabolic engineering strategy and a process basis for efficient microbial production of L-histidine.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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