Molecular and Biochemical Studies of Chondramide Formation-Highly Cytotoxic Natural Products from Chondromyces crocatus Cm c5

Shwan Rachid; Daniel Krug; Brigitte Kunze; Irene Kochems; Maren Scharfe; T. Mark Zabriskie; Helmut Blöcker; Rolf Müller

doi:10.1016/j.chembiol.2006.06.002

Molecular and Biochemical Studies of Chondramide Formation-Highly Cytotoxic Natural Products from Chondromyces crocatus Cm c5

Shwan Rachid, Daniel Krug, Brigitte Kunze, Irene Kochems, Maren Scharfe, T. Mark Zabriskie, Helmut Blöcker, Rolf Müller

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

85 Scopus citations

Abstract

The jaspamide/chondramide family of depsipeptides are mixed PKS/NRPS natural products isolated from marine sponges and a terrestrial myxobacterium that potently affect the function of the actin cytoskeleton. As a first step to improve production in heterologous host cells and permit genetic approaches to novel analogs, we have cloned and characterized the chondramide biosynthetic genes from the myxobacterium Chondromyces crocatus Cm c5. In addition to the expected PKS and NRPS genes, the cluster encodes a rare tyrosine aminomutase for β-tyrosine formation and a previously unknown tryptophan-2-halogenase. Conditions for gene transfer into C. crocatus Cm c5 were developed, and inactivation of several genes corroborated their proposed function and served to define the boundaries of the cluster. Biochemical characterization of the final NRPS adenylation domain confirmed the direct activation of β-tyrosine, and fluorinated chondramides were produced through precursor-directed biosynthesis.

Original language	English (US)
Pages (from-to)	667-681
Number of pages	15
Journal	Chemistry and Biology
Volume	13
Issue number	6
DOIs	https://doi.org/10.1016/j.chembiol.2006.06.002
State	Published - Jun 2006
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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@article{93f24ace9ed149ce871904695ea91af7,

title = "Molecular and Biochemical Studies of Chondramide Formation-Highly Cytotoxic Natural Products from Chondromyces crocatus Cm c5",

abstract = "The jaspamide/chondramide family of depsipeptides are mixed PKS/NRPS natural products isolated from marine sponges and a terrestrial myxobacterium that potently affect the function of the actin cytoskeleton. As a first step to improve production in heterologous host cells and permit genetic approaches to novel analogs, we have cloned and characterized the chondramide biosynthetic genes from the myxobacterium Chondromyces crocatus Cm c5. In addition to the expected PKS and NRPS genes, the cluster encodes a rare tyrosine aminomutase for β-tyrosine formation and a previously unknown tryptophan-2-halogenase. Conditions for gene transfer into C. crocatus Cm c5 were developed, and inactivation of several genes corroborated their proposed function and served to define the boundaries of the cluster. Biochemical characterization of the final NRPS adenylation domain confirmed the direct activation of β-tyrosine, and fluorinated chondramides were produced through precursor-directed biosynthesis.",

author = "Shwan Rachid and Daniel Krug and Brigitte Kunze and Irene Kochems and Maren Scharfe and Zabriskie, {T. Mark} and Helmut Bl{\"o}cker and Rolf M{\"u}ller",

note = "Funding Information: The authors would like to thank Y. Elnakady for fluorescense microscopic images. Research in R.M.'s laboratory was funded by the Bundesministerium f{\"u}r Bildung und Forschung and the Deutsche Forschungsgemeinschaft. ",

year = "2006",

month = jun,

doi = "10.1016/j.chembiol.2006.06.002",

language = "English (US)",

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pages = "667--681",

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AU - Rachid, Shwan

AU - Krug, Daniel

AU - Kunze, Brigitte

AU - Kochems, Irene

AU - Scharfe, Maren

AU - Zabriskie, T. Mark

AU - Blöcker, Helmut

AU - Müller, Rolf

N1 - Funding Information: The authors would like to thank Y. Elnakady for fluorescense microscopic images. Research in R.M.'s laboratory was funded by the Bundesministerium für Bildung und Forschung and the Deutsche Forschungsgemeinschaft.

PY - 2006/6

Y1 - 2006/6

N2 - The jaspamide/chondramide family of depsipeptides are mixed PKS/NRPS natural products isolated from marine sponges and a terrestrial myxobacterium that potently affect the function of the actin cytoskeleton. As a first step to improve production in heterologous host cells and permit genetic approaches to novel analogs, we have cloned and characterized the chondramide biosynthetic genes from the myxobacterium Chondromyces crocatus Cm c5. In addition to the expected PKS and NRPS genes, the cluster encodes a rare tyrosine aminomutase for β-tyrosine formation and a previously unknown tryptophan-2-halogenase. Conditions for gene transfer into C. crocatus Cm c5 were developed, and inactivation of several genes corroborated their proposed function and served to define the boundaries of the cluster. Biochemical characterization of the final NRPS adenylation domain confirmed the direct activation of β-tyrosine, and fluorinated chondramides were produced through precursor-directed biosynthesis.

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Molecular and Biochemical Studies of Chondramide Formation-Highly Cytotoxic Natural Products from Chondromyces crocatus Cm c5

Abstract

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