Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria

Avena C. Ross; Ying Xü; Liang Lu; Roland D. Kersten; Zongze Shao; Abdulaziz M. Al-Suwailem; Pieter C. Dorrestein; Pei-Yuan Qian; Bradley S. Moore

doi:10.1021/ja3119674

Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria

Avena C. Ross, Ying Xü, Liang Lu, Roland D. Kersten, Zongze Shao, Abdulaziz M. Al-Suwailem, Pieter C. Dorrestein, Pei-Yuan Qian, Bradley S. Moore

Coastal and Marine Laboratory

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1155-1162
Number of pages	8
Journal	Journal of the American Chemical Society
Volume	135
Issue number	3
DOIs	https://doi.org/10.1021/ja3119674
State	Published - Dec 27 2012

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: 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.).

ASJC Scopus subject areas

Biochemistry
Colloid and Surface Chemistry
General Chemistry
Catalysis

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/ja3119674

https://repository.kaust.edu.sa/bitstream/10754/562616/1/Biosynthetic%20multitasking.pdf

Cite this

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title = "Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria",

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. {\textcopyright} 2012 American Chemical Society.",

author = "Ross, {Avena C.} and Ying X{\"u} and Liang Lu and Kersten, {Roland D.} and Zongze Shao and Al-Suwailem, {Abdulaziz M.} and Dorrestein, {Pieter C.} and Pei-Yuan Qian and Moore, {Bradley S.}",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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.).",

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doi = "10.1021/ja3119674",

language = "English (US)",

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T1 - Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria

AU - Ross, Avena C.

AU - Xü, Ying

AU - Lu, Liang

AU - Kersten, Roland D.

AU - Shao, Zongze

AU - Al-Suwailem, Abdulaziz M.

AU - Dorrestein, Pieter C.

AU - Qian, Pei-Yuan

AU - Moore, Bradley S.

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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.).

PY - 2012/12/27

Y1 - 2012/12/27

N2 - 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.

AB - 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.

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UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563429

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U2 - 10.1021/ja3119674

DO - 10.1021/ja3119674

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C2 - 23270364

SN - 0002-7863

VL - 135

SP - 1155

EP - 1162

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 3

ER -

Biosynthetic multitasking facilitates thalassospiramide structural diversity in marine bacteria

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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