Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria

Handle URI:
http://hdl.handle.net/10754/562616
Title:
Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria
Authors:
Ross, Avena C.; Xü, Ying; Lu, Liang; Kersten, Roland D.; Shao, Zongze; Al-Suwailem, Abdulaziz M.; Dorrestein, Pieter C.; Qian, Peiyuan; Moore, Bradley S.
Abstract:
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.
KAUST Department:
Coastal and Marine Resources Core Lab; Red Sea Research Center (RSRC)
Publisher:
American Chemical Society
Journal:
Journal of the American Chemical Society
Issue Date:
23-Jan-2013
DOI:
10.1021/ja3119674
PubMed ID:
23270364
PubMed Central ID:
PMC3563429
Type:
Article
ISSN:
00027863
Sponsors:
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.).
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563429
Appears in Collections:
Articles; Red Sea Research Center (RSRC); Coastal and Marine Resources Core Lab

Full metadata record

DC FieldValue Language
dc.contributor.authorRoss, Avena C.en
dc.contributor.authorXü, Yingen
dc.contributor.authorLu, Liangen
dc.contributor.authorKersten, Roland D.en
dc.contributor.authorShao, Zongzeen
dc.contributor.authorAl-Suwailem, Abdulaziz M.en
dc.contributor.authorDorrestein, Pieter C.en
dc.contributor.authorQian, Peiyuanen
dc.contributor.authorMoore, Bradley S.en
dc.date.accessioned2015-08-03T10:58:30Zen
dc.date.available2015-08-03T10:58:30Zen
dc.date.issued2013-01-23en
dc.identifier.issn00027863en
dc.identifier.pmid23270364en
dc.identifier.doi10.1021/ja3119674en
dc.identifier.urihttp://hdl.handle.net/10754/562616en
dc.description.abstractThalassospiramides 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.en
dc.description.sponsorshipThe 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.).en
dc.publisherAmerican Chemical Societyen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563429en
dc.titleBiosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteriaen
dc.typeArticleen
dc.contributor.departmentCoastal and Marine Resources Core Laben
dc.contributor.departmentRed Sea Research Center (RSRC)en
dc.identifier.journalJournal of the American Chemical Societyen
dc.identifier.pmcidPMC3563429en
dc.contributor.institutionCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, San Diego, CA 92037, United Statesen
dc.contributor.institutionDivision of Life Science, School of Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Hong Kongen
dc.contributor.institutionThird Institute of Oceanography, China Ocean Administration, Xiemen, Chinaen
dc.contributor.institutionSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, San Diego, CA 92093, United Statesen
kaust.authorAl-Suwailem, Abdulaziz M.en

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