Efficient bioproduction of 5-aminolevulinic acid, a promising biostimulant and nutrient, from renewable bioresources by engineered Corynebacterium glutamicum

Autor: Jiuzhou Chen, Yu Wang, Xuan Guo, Deming Rao, Wenjuan Zhou, Ping Zheng, Jibin Sun, Yanhe Ma
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Biotechnology for Biofuels, Vol 13, Iss 1, Pp 1-13 (2020)
Druh dokumentu: article
ISSN: 1754-6834
DOI: 10.1186/s13068-020-01685-0
Popis: Abstract Background 5-Aminolevulinic acid (5-ALA) is a promising biostimulant, feed nutrient, and photodynamic drug with wide applications in modern agriculture and therapy. Considering the complexity and low yield of chemical synthesis methods, bioproduction of 5-ALA has drawn intensive attention recently. However, the present bioproduction processes use refined glucose as the main carbon source and the production level still needs further enhancement. Results To lay a solid technological foundation for large-scale commercialized bioproduction of 5-ALA, an industrial workhorse Corynebacterium glutamicum was metabolically engineered for high-level 5-ALA biosynthesis from cheap renewable bioresources. After evaluation of 5-ALA synthetases from different sources, the 5-ALA biosynthetic pathway and anaplerotic pathway were rebalanced by regulating intracellular activities of 5-ALA synthetase and phosphoenolpyruvate carboxylase. The engineered biocatalyst produced 5.5 g/L 5-ALA in shake flasks and 16.3 g/L in 5-L bioreactors with a one-step fermentation process from glucose. To lower the cost of feedstock, cheap raw materials were used to replace glucose. Enzymatically hydrolyzed cassava bagasse was proven to be a perfect alternative to refined sugars since the final 5-ALA titer further increased to 18.5 g/L. Use of corn starch hydrolysate resulted in a similar 5-ALA production level (16.0 g/L) with glucose, whereas use of beet molasses caused seriously inhibition. The results obtained here represent a new record of 5-ALA bioproduction. It is estimated that replacing glucose with cassava bagasse will reduce the carbon source cost by 90.1%. Conclusions The high-level biosynthesis of 5-ALA from cheap bioresources will brighten the prospects for industrialization of this sustainable and environment-friendly process. The strategy for balancing metabolic flux developed in this study can also be used for improving the bioproduction of other value-added chemicals.
Databáze: Directory of Open Access Journals
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