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Cultivation-independent approaches to investigate the chemistry of marine symbiotic bacteria

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Abstract

Sessile marine animals like sponges, tunicates, and bryozoans are a rich source of bioactive natural products, many of which exhibit potent anticancer activities. However, most of these substances are available in very limited amounts only, which has prohibited further drug development. Recent evidence suggests that symbiotic bacteria might be the true producers of many animal-derived metabolites. In addition to revealing fascinating perspectives for research in marine chemical ecology, these findings suggest new solutions to the supply problem. Although most symbionts remain uncultivated, bacterial production systems might be created by isolating biosynthetic genes from marine metagenomes, and expressing them in culturable bacterial hosts. This review discusses cell-sorting, natural product visualization, and phylogenetic approaches to identify symbiotic producers. In addition, strategies to isolate genes and gene clusters from marine species consortia are described. These techniques have provided insights into the bacterial origin and biosynthesis of polyketides like the onnamides, swinholides, and bryostatins, of peptides including the patellamides, chlorinated dipeptides, and theopalauamide as well as of brominated biphenylethers.

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Abbreviations

BAC:

Bacterial artificial chromosome

CARD-FISH:

Catalyzed reporter deposition fluorescence in situ hybridization

CMF-ASW:

Calcium–magnesium-free artificial sea water

CoA:

Coenzyme A

DGGE:

Denaturing gradient gel electrophoresis

FACS:

Fluorescence-activated cell-sorting

FISH:

Fluorescence in situ hybridization

HRP:

Horseradish peroxidase

MALDI-TOF MS:

Matrix-assisted laser desorption ionization–time of flight mass spectrometry

NRPS:

Nonribosomal peptide synthetase

PAC:

P1-derived artificial chromosome

PKS:

Polyketide synthase

SSCP:

Single-strand conformation polymorphism analysis

YAC:

Yeast artificial chromosome

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Acknowledgments

Work on marine symbiosis in the authors’ laboratory was funded by grants of the DFG (PI 430/1-1 to 1-3, PI 430/2-1 to 2-2, PI 430/5-1 to 5-2, PI 430/6-1), the JSPS and the BMBF (03F0414F) to J.P. and a DAAD scholarship to A. U. We thank S. Matsunaga, N. Fusetani, U. Hentschel, P. Crews, M. Munro, J. Blunt, M. Platzer, V. Webb, R. Quinn, B. S. Moore and W. Boland for collaborative opportunities and support.

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  1. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany

    Agustinus Uria & Jörn Piel

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  1. Agustinus Uria
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  2. Jörn Piel
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Correspondence to Jörn Piel.

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Uria, A., Piel, J. Cultivation-independent approaches to investigate the chemistry of marine symbiotic bacteria. Phytochem Rev 8, 401–414 (2009). https://doi.org/10.1007/s11101-009-9127-7

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