2. Academic Validation
  3. Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from Hapsidospora irregularis

Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from Hapsidospora irregularis

  • J Nat Prod. 2017 Feb 24;80(2):363-370. doi: 10.1021/acs.jnatprod.6b00808.
Shuwei Zhang 1,  Yixing Qiu 1 2,  Thomas B Kakule,  Zhenyu Lu,  Fuchao Xu 1,  John G Lamb,  Christopher A Reilly,  Yong Zheng 3,  Shing Wo Simon Sham 4,  Wei Wang 2,  Lijiang Xuan 3,  Eric W Schmidt,  Jixun Zhan 1 2
Affiliations

Affiliations

  • 1 Department of Biological Engineering, Utah State University , 4105 Old Main Hill, Logan, Utah 84322, United States.
  • 2 TCM and Ethnomedicine Innovation & Development Laboratory, School of Pharmacy, Hunan University of Chinese Medicine , Changsha, Hunan 410208, People's Republic of China.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 202203, People's Republic of China.
  • 4 Department of Chemistry and Biochemistry, Utah State University , 0300 Old Main Hill, Logan, Utah 84322, United States.
PMID: 28106998 DOI: 10.1021/acs.jnatprod.6b00808
Abstract

Seven cyclic depsipeptides were isolated from Hapsidospora irregularis and structurally characterized as the Calcium Channel blocker leualacin and six new analogues based on the NMR and HRESIMS data. These new compounds were named leualacins B-G. The absolute configurations of the Amino acids and 2-hydroxyisocaproic acids were determined by recording the optical rotation values. Biological studies showed that calcium influx elicited by leualacin F in primary human lobar bronchial epithelial cells involves the TRPA1 channel. Through genome Sequencing and targeted gene disruption, a noniterative nonribosomal peptide synthetase was found to be involved in the biosynthesis of leualacin. A comparison of the structures of leualacin and its analogues indicated that the A2 and A4 domains of the leualacin synthetase are substrate specific, while A1, A3, and A5 can accept alternative precursors to yield new molecules.

Figures
Products