Elucidating the biosynthetic pathway for the polyketide-nonribosomal peptide collismycin A: Mechanism for formation of the 2,2′-bipyridyl ring

Ignacio Garcia; Natalia M. Vior; Alfredo F. Braña; Javier González-Sabin; Jürgen Rohr; Francisco Moris; Carmen Méndez; José A. Salas

doi:10.1016/j.chembiol.2012.01.014

Elucidating the biosynthetic pathway for the polyketide-nonribosomal peptide collismycin A: Mechanism for formation of the 2,2′-bipyridyl ring

Ignacio Garcia, Natalia M. Vior, Alfredo F. Braña, Javier González-Sabin, Jürgen Rohr, Francisco Moris, Carmen Méndez, José A. Salas

Pharmaceutical Sciences

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

47 Scopus citations

Abstract

The gene cluster for the bipyridyl compound collismycin was characterized from Streptomyces sp. CS40. Sequence analysis of a 46.7 kb DNA region revealed 27 open reading frames, 23 of which are involved in collismycin biosynthesis. Eight insertional inactivation mutants were generated in the sequenced region to prove its involvement in collismycin biosynthesis, define the boundaries of the cluster, functionally characterize some genes, and isolate two biosynthetic intermediates. A model for collismycin biosynthesis - which includes the conversion of lysine into picolinic acid, participation of a polyketide synthase-non-ribosomal peptide synthetase system, and some further modifications - is proposed. The biosynthetic pathway would include an unusual NRPS-mediated incorporation of a cysteine residue, possibly through a Michael addition and followed by the extension of the peptide chain by leucine incorporation and later removal by amidohydrolase.

Original language	English
Pages (from-to)	399-413
Number of pages	15
Journal	Chemistry and Biology
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/j.chembiol.2012.01.014
State	Published - Mar 23 2012

Bibliographical note

Funding Information:
We wish to thank Carlos Olano and Jesús Cortes for a critical reading of our manuscript. This research was supported by a Spanish Ministry of Science and Innovation grant (BIO2009-07643) and the Red Temática de Investigación Cooperativa de Centros de Cáncer (Ministry of Health, ISCIII-RETIC RD06/0020/0026 to J.A.S). We thank the Spanish Ministry of Science and Innovation for the PhD student fellowship (F.P.U.) to Natalia M. Vior.

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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10.1016/j.chembiol.2012.01.014

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title = "Elucidating the biosynthetic pathway for the polyketide-nonribosomal peptide collismycin A: Mechanism for formation of the 2,2′-bipyridyl ring",

abstract = "The gene cluster for the bipyridyl compound collismycin was characterized from Streptomyces sp. CS40. Sequence analysis of a 46.7 kb DNA region revealed 27 open reading frames, 23 of which are involved in collismycin biosynthesis. Eight insertional inactivation mutants were generated in the sequenced region to prove its involvement in collismycin biosynthesis, define the boundaries of the cluster, functionally characterize some genes, and isolate two biosynthetic intermediates. A model for collismycin biosynthesis - which includes the conversion of lysine into picolinic acid, participation of a polyketide synthase-non-ribosomal peptide synthetase system, and some further modifications - is proposed. The biosynthetic pathway would include an unusual NRPS-mediated incorporation of a cysteine residue, possibly through a Michael addition and followed by the extension of the peptide chain by leucine incorporation and later removal by amidohydrolase.",

author = "Ignacio Garcia and Vior, {Natalia M.} and Bra{\~n}a, {Alfredo F.} and Javier Gonz{\'a}lez-Sabin and J{\"u}rgen Rohr and Francisco Moris and Carmen M{\'e}ndez and Salas, {Jos{\'e} A.}",

note = "Funding Information: We wish to thank Carlos Olano and Jes{\'u}s Cortes for a critical reading of our manuscript. This research was supported by a Spanish Ministry of Science and Innovation grant (BIO2009-07643) and the Red Tem{\'a}tica de Investigaci{\'o}n Cooperativa de Centros de C{\'a}ncer (Ministry of Health, ISCIII-RETIC RD06/0020/0026 to J.A.S). We thank the Spanish Ministry of Science and Innovation for the PhD student fellowship (F.P.U.) to Natalia M. Vior. ",

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AU - Garcia, Ignacio

AU - Vior, Natalia M.

AU - Braña, Alfredo F.

AU - González-Sabin, Javier

AU - Rohr, Jürgen

AU - Moris, Francisco

AU - Méndez, Carmen

AU - Salas, José A.

N1 - Funding Information: We wish to thank Carlos Olano and Jesús Cortes for a critical reading of our manuscript. This research was supported by a Spanish Ministry of Science and Innovation grant (BIO2009-07643) and the Red Temática de Investigación Cooperativa de Centros de Cáncer (Ministry of Health, ISCIII-RETIC RD06/0020/0026 to J.A.S). We thank the Spanish Ministry of Science and Innovation for the PhD student fellowship (F.P.U.) to Natalia M. Vior.

PY - 2012/3/23

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Elucidating the biosynthetic pathway for the polyketide-nonribosomal peptide collismycin A: Mechanism for formation of the 2,2′-bipyridyl ring

Abstract

Bibliographical note

ASJC Scopus subject areas

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