Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria
Name:
Biosynthetic multitasking.pdf
Size:
1.453Mb
Format:
PDF
Description:
Accepted manuscript
Type
ArticleAuthors
Ross, Avena C.Xü, Ying
Lu, Liang
Kersten, Roland D.
Shao, Zongze
Al-Suwailem, Abdulaziz M.
Dorrestein, Pieter C.
Qian, Pei-Yuan

Moore, Bradley S.
KAUST Department
Coastal and Marine Resources Core LabRed Sea Research Center (RSRC)
Date
2012-12-27Online Publication Date
2013-01-11Print Publication Date
2013-01-23Embargo End Date
2013-12-27Permanent link to this record
http://hdl.handle.net/10754/562616
Metadata
Show full item recordAbstract
Thalassospiramides A and B are immunosuppressant cyclic lipopeptides first reported from the marine α-proteobacterium Thalassospira sp. CNJ-328. We describe here the discovery and characterization of an extended family of 14 new analogues from four Tistrella and Thalassospira isolates. These potent calpain 1 protease inhibitors belong to six structure classes in which the length and composition of the acylpeptide side chain varies extensively. Genomic sequence analysis of the thalassospiramide-producing microbes revealed related, genus-specific biosynthetic loci encoding hybrid nonribosomal peptide synthetase/polyketide synthases consistent with thalassospiramide assembly. The bioinformatics analysis of the gene clusters suggests that structural diversity, which ranges from the 803.4 Da thalassospiramide C to the 1291.7 Da thalassospiramide F, results from a complex sequence of reactions involving amino acid substrate channeling and enzymatic multimodule skipping and iteration. Preliminary biochemical analysis of the N-terminal nonribosomal peptide synthetase module from the Thalassospira TtcA megasynthase supports a biosynthetic model in which in cis amino acid activation competes with in trans activation to increase the range of amino acid substrates incorporated at the N terminus. © 2012 American Chemical Society.Citation
Ross, A. C., Xu, Y., Lu, L., Kersten, R. D., Shao, Z., Al-Suwailem, A. M., … Moore, B. S. (2013). Biosynthetic Multitasking Facilitates Thalassospiramide Structural Diversity in Marine Bacteria. Journal of the American Chemical Society, 135(3), 1155–1162. doi:10.1021/ja3119674Sponsors
The authors gratefully acknowledge W. Fenical from UCSD for Thalassospira sp. CNJ-328 and E Mann from the Skidaway Institute of Oceanography for Thalassospira sp. TrichSKD 10. Tistrella bauzanensis TIO7329 was generously provided from the Third Institute of Oceanography, China PRC. J. P. Noel at the Salk Institute for Biological Sciences kindly provided access to the Ion Torrent sequencing instrument. Financial support was provided by the China Ocean Mineral Resources Research and Development Association (DY125-15-T-02), the King Abdullah University of Science and Technology (SA-00040/UK-00016 to P.Y.Q,), and the NIH (GM97509 to B.S.M. and P.C.D.).Publisher
American Chemical Society (ACS)PubMed ID
23270364PubMed Central ID
PMC3563429Additional Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563429http://europepmc.org/articles/pmc3563429?pdf=render
ae974a485f413a2113503eed53cd6c53
10.1021/ja3119674
Scopus Count
Related articles
- Thalassospiramides A and B, immunosuppressive peptides from the marine bacterium Thalassospira sp.
- Authors: Oh DC, Strangman WK, Kauffman CA, Jensen PR, Fenical W
- Issue date: 2007 Apr 12
- Thalassospiramide G, a new γ-amino-acid-bearing peptide from the marine bacterium Thalassospira sp.
- Authors: Um S, Pyee Y, Kim EH, Lee SK, Shin J, Oh DC
- Issue date: 2013 Feb 26
- Mechanism of action of thalassospiramides, a new class of calpain inhibitors.
- Authors: Lu L, Meehan MJ, Gu S, Chen Z, Zhang W, Zhang G, Liu L, Huang X, Dorrestein PC, Xu Y, Moore BS, Qian PY
- Issue date: 2015 Mar 5
- Family-wide Structural Characterization and Genomic Comparisons Decode the Diversity-oriented Biosynthesis of Thalassospiramides by Marine Proteobacteria.
- Authors: Zhang W, Lu L, Lai Q, Zhu B, Li Z, Xu Y, Shao Z, Herrup K, Moore BS, Ross AC, Qian PY
- Issue date: 2016 Dec 30
- Pass-back chain extension expands multimodular assembly line biosynthesis.
- Authors: Zhang JJ, Tang X, Huan T, Ross AC, Moore BS
- Issue date: 2020 Jan