title: Overexpression of the Global Regulator LaeA in Chaetomium globosum Leads to the Biosynthesis of Chaetoglobosin Z.
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.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Menghua
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Beijing 100050, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jinguang
authors.initials: J
authors.lastname: Si
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Cao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Institute of Microbiology, Chinese Academy of Sciences , Beijing 100090, People's Republic of China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory for Applied Microbiology of Shandong Province , Jinan 250014, People's Republic of China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zou
mesh_terms: D002597:Chaetomium / Q000737:chemistry* / Q000235:genetics; D002681:China; D056945:Hep G2 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D016133:Polymerase Chain Reaction
chemical_list: D026121:Indole Alkaloids; C019290:chaetoglobosins