Engineering the biosynthesis of the polyketide-nonribosomal peptide collismycin A for generation of analogs with neuroprotective activity

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

doi:10.1016/j.chembiol.2013.06.014

Engineering the biosynthesis of the polyketide-nonribosomal peptide collismycin A for generation of analogs with neuroprotective activity

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

Producción científica: Article › revisión exhaustiva

38 Citas (Scopus)

Resumen

Collismycin A is a member of the 2,2′-bipyridyl family of natural products that shows cytotoxic activity. Structurally, it belongs to the hybrid polyketides-nonribosomal peptides. After the isolation and characterization of the collismycin A gene cluster, we have used the combination of two different approaches (insertional inactivation and biocatalysis) to increase structural diversity in this natural product class. Twelve collismycin analogs were generated with modifications in the second pyridine ring of collismycin A, thus potentially maintaining biologic activity. None of these analogs showed better cytotoxic activity than the parental collismycin. However, some analogs showed neuroprotective activity and one of them (collismycin H) showed better values for neuroprotection against oxidative stress in a zebrafish model than those of collismycin A. Interestingly, this analog also showed very poor cytotoxic activity, a feature very desirable for a neuroprotectant compound.

Idioma original	English
Páginas (desde-hasta)	1022-1032
Número de páginas	11
Publicación	Chemistry and Biology
Volumen	20
N.º	8
DOI	https://doi.org/10.1016/j.chembiol.2013.06.014
Estado	Published - ago 22 2013

Nota bibliográfica

Funding Information:
This research was supported by a grant (to J.A.S.) from the Spanish Ministry of Science and Innovation (BIO2009-07643) and the Plan Regional de Investigación del Principado de Asturias (PC10-05). N.V. was the recipient of a predoctoral fellowship of the Spanish Ministry of Science and Innovation (MICINN, FPI). We are very grateful to Carlos Olano for helpful discussions. We would like to thank Marcos Garcia Ocaña and ZFBiolabs (Madrid, Spain) for helping with the cytotoxicity and zebrafish assays, respectively.

Financiación

This research was supported by a grant (to J.A.S.) from the Spanish Ministry of Science and Innovation (BIO2009-07643) and the Plan Regional de Investigación del Principado de Asturias (PC10-05). N.V. was the recipient of a predoctoral fellowship of the Spanish Ministry of Science and Innovation (MICINN, FPI). We are very grateful to Carlos Olano for helpful discussions. We would like to thank Marcos Garcia Ocaña and ZFBiolabs (Madrid, Spain) for helping with the cytotoxicity and zebrafish assays, respectively.

Financiadores	Número del financiador
Plan Regional de Investigación del Principado de Asturias	PC10-05
Family Process Institute Incorporated
Ministerio de Ciencia, Innovación y Universidades	BIO2009-07643

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

Acceder al documento

10.1016/j.chembiol.2013.06.014

Otros archivos y enlaces

Citar esto

@article{067693de3c91427e9329d2112161f862,

title = "Engineering the biosynthesis of the polyketide-nonribosomal peptide collismycin A for generation of analogs with neuroprotective activity",

abstract = "Collismycin A is a member of the 2,2′-bipyridyl family of natural products that shows cytotoxic activity. Structurally, it belongs to the hybrid polyketides-nonribosomal peptides. After the isolation and characterization of the collismycin A gene cluster, we have used the combination of two different approaches (insertional inactivation and biocatalysis) to increase structural diversity in this natural product class. Twelve collismycin analogs were generated with modifications in the second pyridine ring of collismycin A, thus potentially maintaining biologic activity. None of these analogs showed better cytotoxic activity than the parental collismycin. However, some analogs showed neuroprotective activity and one of them (collismycin H) showed better values for neuroprotection against oxidative stress in a zebrafish model than those of collismycin A. Interestingly, this analog also showed very poor cytotoxic activity, a feature very desirable for a neuroprotectant compound.",

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

note = "Funding Information: This research was supported by a grant (to J.A.S.) from the Spanish Ministry of Science and Innovation (BIO2009-07643) and the Plan Regional de Investigaci{\'o}n del Principado de Asturias (PC10-05). N.V. was the recipient of a predoctoral fellowship of the Spanish Ministry of Science and Innovation (MICINN, FPI). We are very grateful to Carlos Olano for helpful discussions. We would like to thank Marcos Garcia Oca{\~n}a and ZFBiolabs (Madrid, Spain) for helping with the cytotoxicity and zebrafish assays, respectively. ",

year = "2013",

month = aug,

day = "22",

doi = "10.1016/j.chembiol.2013.06.014",

language = "English",

volume = "20",

pages = "1022--1032",

number = "8",

}

TY - JOUR

T1 - Engineering the biosynthesis of the polyketide-nonribosomal peptide collismycin A for generation of analogs with neuroprotective activity

AU - Garcia, Ignacio

AU - Vior, Natalia M.

AU - González-Sabín, Javier

AU - Braña, Alfredo F.

AU - Rohr, Jürgen

AU - Moris, Francisco

AU - Méndez, Carmen

AU - Salas, José A.

N1 - Funding Information: This research was supported by a grant (to J.A.S.) from the Spanish Ministry of Science and Innovation (BIO2009-07643) and the Plan Regional de Investigación del Principado de Asturias (PC10-05). N.V. was the recipient of a predoctoral fellowship of the Spanish Ministry of Science and Innovation (MICINN, FPI). We are very grateful to Carlos Olano for helpful discussions. We would like to thank Marcos Garcia Ocaña and ZFBiolabs (Madrid, Spain) for helping with the cytotoxicity and zebrafish assays, respectively.

PY - 2013/8/22

Y1 - 2013/8/22

N2 - Collismycin A is a member of the 2,2′-bipyridyl family of natural products that shows cytotoxic activity. Structurally, it belongs to the hybrid polyketides-nonribosomal peptides. After the isolation and characterization of the collismycin A gene cluster, we have used the combination of two different approaches (insertional inactivation and biocatalysis) to increase structural diversity in this natural product class. Twelve collismycin analogs were generated with modifications in the second pyridine ring of collismycin A, thus potentially maintaining biologic activity. None of these analogs showed better cytotoxic activity than the parental collismycin. However, some analogs showed neuroprotective activity and one of them (collismycin H) showed better values for neuroprotection against oxidative stress in a zebrafish model than those of collismycin A. Interestingly, this analog also showed very poor cytotoxic activity, a feature very desirable for a neuroprotectant compound.

AB - Collismycin A is a member of the 2,2′-bipyridyl family of natural products that shows cytotoxic activity. Structurally, it belongs to the hybrid polyketides-nonribosomal peptides. After the isolation and characterization of the collismycin A gene cluster, we have used the combination of two different approaches (insertional inactivation and biocatalysis) to increase structural diversity in this natural product class. Twelve collismycin analogs were generated with modifications in the second pyridine ring of collismycin A, thus potentially maintaining biologic activity. None of these analogs showed better cytotoxic activity than the parental collismycin. However, some analogs showed neuroprotective activity and one of them (collismycin H) showed better values for neuroprotection against oxidative stress in a zebrafish model than those of collismycin A. Interestingly, this analog also showed very poor cytotoxic activity, a feature very desirable for a neuroprotectant compound.

UR - https://www.scopus.com/pages/publications/84883147489

UR - https://www.scopus.com/pages/publications/84883147489#tab=citedBy

U2 - 10.1016/j.chembiol.2013.06.014

DO - 10.1016/j.chembiol.2013.06.014

M3 - Article

C2 - 23911584

AN - SCOPUS:84883147489

SN - 1074-5521

VL - 20

SP - 1022

EP - 1032

JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 8

ER -

Engineering the biosynthesis of the polyketide-nonribosomal peptide collismycin A for generation of analogs with neuroprotective activity

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto