Overexpression of the Global Regulator LaeA in Chaetomium globosum Leads to the Biosynthesis of Chaetoglobosin Z

  • J Nat Prod. 2016 Oct 28;79(10):2487-2494. doi: 10.1021/acs.jnatprod.6b00333.
Tao Jiang  1 ,  Menghua Wang  1 ,  Li Li  2 ,  Jinguang Si  1  3 ,  Bo Song  1 ,  Cao Zhou  1 ,  Meng Yu  1 ,  Xuewei Wang  4 ,  Yonggang Zhang  5 ,  Gang Ding  1  2 ,  Zhongmei Zou  1
Affiliations
  • 1. 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.
  • 2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica , Beijing 100050, People's Republic of China.
  • 3. School of Pharmacy, Henan University of Traditional Chinese Medicine , Zhengzhou 450046, People's Republic of China.
  • 4. Institute of Microbiology, Chinese Academy of Sciences , Beijing 100090, People's Republic of China.
  • 5. Key Laboratory for Applied Microbiology of Shandong Province , Jinan 250014, People's Republic of China.
PMID: 27759375 DOI: 10.1021/acs.jnatprod.6b00333
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.