Co-addition Strategy for Enhancement of Chaetominine from Submerged Fermentation of Aspergillus fumigatus CY018
- 16 Downloads
Chaetominine (CHA), a novel framework tripeptide alkaloid, imparts an attractive cytotoxic against the human leukemia cell line K562, which is produced by Aspergillus fumigatus CY018. However, its pharmacological research is restricted by low yields in submerged culture, which needs to be resolved immediately by biotechnology. In this work, a co-addition strategy was applied to promote CHA production based on related inhibitors’ addition and precursors’ addition, inspired by the biosynthetic pathway analysis of CHA. CHA production reached 53.87 mg/L by addition of 10 mM shikimate, 10 mM anthranilate, 20 mM tryptophan, and 10 mM alanine in shake flask. Compared to the control without addition of precursors, the activity of 3-deoxy-arabino-heptulosonate-7-phospahte (DAHP) synthase was significantly improved and the transcription levels of critical genes in shikimate pathway were up-regulated responded to the co-addition of precursors. The improvement of CHA production by co-addition of precursors was also successfully reproduced in the lab-scale bioreactor (5-L) system, in which CHA production reached 46.10 mg/L. This work demonstrated that precursors’ co-addition was an effective strategy for increasing CHA production, and the information obtained might be useful to the further improvement of CHA on a large scale.
KeywordsChaetominine Aspergillus fumigatus Shikimate pathway Co-addition strategy Submerged fermentation
This work was supported by the National Natural Science Foundation of China (No. 81741156), the Shanghai Sailing Program (17YF1403700), and the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 4.Gui, R. Y., Xu, L., Kuang, Y., Chung, L. M., Qin, J. C., Liu, L., Yang, S. X., & Zhao, L. C. (2015). Chaetominine, (+)-alantrypinone, questin, isorhodoptilometrin, and 4-hydroxybenzaldehyde produced by the endophytic fungus Aspergillus sp. YL-6 inhibit wheat (Triticum aestivum) and radish (Raphanus sativus) germination. Journal of Plant Interactions, 10, 87–92.CrossRefGoogle Scholar
- 13.Mao, X. Z., Wang, F., Zhang, J. G., Chen, S., Deng, Z. X., Shen, Y. L., & Wei, D. Z. (2009). The pH shift and precursor feeding strategy in a low-toxicity FR-008/Candicidin derivative CS103 fermentation bioprocess by a mutant of Streptomyces sp. FR-008. Applied Biochemistry and Biotechnology, 159(3), 673–686.CrossRefGoogle Scholar
- 21.Sun, X. Q., Zhou, X. S., Cai, M. H., Tao, K. J., & Zhang, Y. X. (2009). Identified biosynthetic pathway of aspergiolide A and a novel strategy to increase its production in a marine-derived fungus Aspergillus glaucus by feeding of biosynthetic precursors and inhibitors simultaneously. Bioresource Technology, 100(18), 4244–4251.CrossRefGoogle Scholar
- 22.Zhang, K., Li, H. D., Chen, W. X., Zhao, M. L., Cui, H. Y., Min, Q. S., Wang, H. J., Chen, S. L., & Li, D. M. (2017). Regulation of the docosapentaenoic acid/docosahexaenoic acid ratio (DPA/DHA ratio) in Schizochytrium limacinum B4D1. Applied Biochemistry and Biotechnology, 182(1), 67–81.CrossRefGoogle Scholar
- 33.Verma, P., Khan, S. A., Mathur, A. K., Ghosh, S., Shanker, K., & Kalra, A. (2014). Improved sanguinarine production via biotic and abiotic elicitations and precursor feeding in cell suspensions of latex-less variety of Papaver somniferum with their gene expression studies and upscaling in bioreactor. Protoplasma, 251(6), 1359–1371.CrossRefGoogle Scholar