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Overexpression of the Global Regulator LaeA in Chaetomium globosum Leads to the Biosynthesis of Chaetoglobosin Z.
J Nat Prod. 2016 10 28; 79(10):2487-2494.JN

Abstract

Overexpression of laeA in Chaetomium globosum CBS148.51 up-regulated expression of the chaetoglobosin gene cluster and resulted in the isolation of a new cytochalasan, chaetoglobosin Z (1), together with six known analogues, chaetoglobosins A (2), B (3), D (4), E (5), O (6), and V (7). RT-PCR analysis confirmed that the key genes in the chaetoglobosin gene cluster were significantly up-regulated. The structure of the new compound chaetoglobosin Z (1) was elucidated using NMR data. The relative and absolute configurations were determined by NOESY and electronic circular dichroism combined with quantum-chemical calculations adopting time-dependent density functional theory methods, respectively. These compounds displayed strong biological effects against the HepG 2 cell line compared with the positive control. The results further supported that LaeA is a global regulator that could up-regulate and/or activate cryptic gene clusters to produce new secondary metabolites.

Authors+Show Affiliations

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China.Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China.State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Beijing 100050, People's Republic of China.Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China. School of Pharmacy, Henan University of Traditional Chinese Medicine , Zhengzhou 450046, People's Republic of China.Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China.Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China.Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China.Institute of Microbiology, Chinese Academy of Sciences , Beijing 100090, People's Republic of China.Key Laboratory for Applied Microbiology of Shandong Province , Jinan 250014, People's Republic of China.Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Beijing 100050, People's Republic of China.Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development , Beijing, 100193, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27759375

Citation

Jiang, Tao, et al. "Overexpression of the Global Regulator LaeA in Chaetomium Globosum Leads to the Biosynthesis of Chaetoglobosin Z." Journal of Natural Products, vol. 79, no. 10, 2016, pp. 2487-2494.
Jiang T, Wang M, Li L, et al. Overexpression of the Global Regulator LaeA in Chaetomium globosum Leads to the Biosynthesis of Chaetoglobosin Z. J Nat Prod. 2016;79(10):2487-2494.
Jiang, T., Wang, M., Li, L., Si, J., Song, B., Zhou, C., Yu, M., Wang, X., Zhang, Y., Ding, G., & Zou, Z. (2016). Overexpression of the Global Regulator LaeA in Chaetomium globosum Leads to the Biosynthesis of Chaetoglobosin Z. Journal of Natural Products, 79(10), 2487-2494.
Jiang T, et al. Overexpression of the Global Regulator LaeA in Chaetomium Globosum Leads to the Biosynthesis of Chaetoglobosin Z. J Nat Prod. 2016 10 28;79(10):2487-2494. PubMed PMID: 27759375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of the Global Regulator LaeA in Chaetomium globosum Leads to the Biosynthesis of Chaetoglobosin Z. AU - Jiang,Tao, AU - Wang,Menghua, AU - Li,Li, AU - Si,Jinguang, AU - Song,Bo, AU - Zhou,Cao, AU - Yu,Meng, AU - Wang,Xuewei, AU - Zhang,Yonggang, AU - Ding,Gang, AU - Zou,Zhongmei, Y1 - 2016/10/19/ PY - 2016/10/30/pubmed PY - 2017/6/18/medline PY - 2016/10/30/entrez SP - 2487 EP - 2494 JF - Journal of natural products JO - J Nat Prod VL - 79 IS - 10 N2 - Overexpression of laeA in Chaetomium globosum CBS148.51 up-regulated expression of the chaetoglobosin gene cluster and resulted in the isolation of a new cytochalasan, chaetoglobosin Z (1), together with six known analogues, chaetoglobosins A (2), B (3), D (4), E (5), O (6), and V (7). RT-PCR analysis confirmed that the key genes in the chaetoglobosin gene cluster were significantly up-regulated. The structure of the new compound chaetoglobosin Z (1) was elucidated using NMR data. The relative and absolute configurations were determined by NOESY and electronic circular dichroism combined with quantum-chemical calculations adopting time-dependent density functional theory methods, respectively. These compounds displayed strong biological effects against the HepG 2 cell line compared with the positive control. The results further supported that LaeA is a global regulator that could up-regulate and/or activate cryptic gene clusters to produce new secondary metabolites. SN - 1520-6025 UR - https://www.unboundmedicine.com/medline/citation/27759375/Overexpression_of_the_Global_Regulator_LaeA_in_Chaetomium_globosum_Leads_to_the_Biosynthesis_of_Chaetoglobosin_Z_ DB - PRIME DP - Unbound Medicine ER -