Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743

Schofield, Michael M.; Jain, Sunit; Porat, Daphne; Dick, Gregory J.; Sherman, David H.

doi:10.1111/1462-2920.12908

Title: Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743

Journal Article · Tue Jul 21 00:00:00 EDT 2015 · Environmental Microbiology

DOI: https://doi.org/10.1111/1462-2920.12908 · OSTI ID:1344906

Schofield, Michael M. ^[1]; Jain, Sunit ^[2]; Porat, Daphne ^[2]; Dick, Gregory J. ^[2]; Sherman, David H. ^[2]

Univ. of Michigan, Ann Arbor, MI (United States); DOE Office of Scientific and Technical Information (OSTI)
Univ. of Michigan, Ann Arbor, MI (United States)

Ecteinascidin 743 (ET-743, Yondelis) is a clinically approved chemotherapeutic natural product isolated from the Caribbean mangrove tunicate Ecteinascidia turbinata. Researchers have long suspected that a microorganism may be the true producer of the anti-cancer drug, but its genome has remained elusive due to our inability to culture the bacterium in the laboratory using standard techniques. Here, we sequenced and assembled the complete genome of the ET-743 producer, Candidatus Endoecteinascidia frumentensis, directly from metagenomic DNA isolated from the tunicate. Analysis of the ~631 kb microbial genome revealed strong evidence of an endosymbiotic lifestyle and extreme genome reduction. Phylogenetic analysis suggested that the producer of the anti-cancer drug is taxonomically distinct from other sequenced microorganisms and could represent a new family of Gammaproteobacteria. The complete genome has also greatly expanded our understanding of ET-743 production and revealed new biosynthetic genes dispersed across more than 173 kb of the small genome. The gene cluster’s architecture and its preservation demonstrate that the drug is likely essential to the interactions of the microorganism with its mangrove tunicate host. In conclusion, taken together, these studies elucidate the lifestyle of a unique, and pharmaceutically-important microorganism and highlight the wide diversity of bacteria capable of making potent natural products.

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Research Organization:: Univ. of Michigan, Ann Arbor, MI (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1344906

Journal Information:: Environmental Microbiology, Journal Name: Environmental Microbiology Journal Issue: 10 Vol. 17; ISSN 1462-2912

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (55)

Horizontal Gene Transfer and the Evolution of Secondary Metabolite Gene Clusters in Fungi: An Hypothesis Walton, Jonathan D. Fungal Genetics and Biology, Vol. 30, Issue 3, p. 167-171 https://doi.org/10.1006/fgbi.2000.1224	journal	August 2000
Chemical defense and aposematic coloration in larvae of the ascidian Ecteinascidia turbinata Young, C. M.; Bingham, B. L. Marine Biology, Vol. 96, Issue 4 https://doi.org/10.1007/BF00397972	journal	December 1987
Intracellular bacteria associated with the ascidian Ecteinascidia turbinata : phylogenetic and in situ hybridisation analysis Moss, C.; Green, D. H.; P�rez, B. Marine Biology, Vol. 143, Issue 1 https://doi.org/10.1007/s00227-003-1060-5	journal	July 2003
Bacterial diversity associated with the Caribbean tunicate Ecteinascidia turbinata Pérez-Matos, Ana E.; Rosado, William; Govind, Nadathur S. Antonie van Leeuwenhoek, Vol. 92, Issue 2 https://doi.org/10.1007/s10482-007-9143-9	journal	January 2007
Core Assembly Mechanism of Quinocarcin/SF-1739: Bimodular Complex Nonribosomal Peptide Synthetases for Sequential Mannich-type Reactions Hiratsuka, Tomoshige; Koketsu, Kento; Minami, Atsushi Chemistry & Biology, Vol. 20, Issue 12 https://doi.org/10.1016/j.chembiol.2013.10.011	journal	December 2013
Defensive Bacteriome Symbiont with a Drastically Reduced Genome Nakabachi, Atsushi; Ueoka, Reiko; Oshima, Kenshiro Current Biology, Vol. 23, Issue 15 https://doi.org/10.1016/j.cub.2013.06.027	journal	August 2013
CLUSEAN: A computer-based framework for the automated analysis of bacterial secondary metabolite biosynthetic gene clusters Weber, T.; Rausch, C.; Lopez, P. Journal of Biotechnology, Vol. 140, Issue 1-2 https://doi.org/10.1016/j.jbiotec.2009.01.007	journal	March 2009
Meta-omic Characterization of the Marine Invertebrate Microbial Consortium That Produces the Chemotherapeutic Natural Product ET-743 Rath, Christopher M.; Janto, Benjamin; Earl, Josh ACS Chemical Biology, Vol. 6, Issue 11 https://doi.org/10.1021/cb200244t	journal	September 2011
Enantioselective Total Synthesis of Ecteinascidin 743 Corey, E. J.; Gin, David Y.; Kania, Robert S. Journal of the American Chemical Society, Vol. 118, Issue 38 https://doi.org/10.1021/ja962480t	journal	January 1996
Ecteinascidins 729, 743, 745, 759A, 759B, and 770: potent antitumor agents from the Caribbean tunicate Ecteinascidia turbinata Rinehart, Kenneth L.; Holt, Tom G.; Fregeau, Nancy L. The Journal of Organic Chemistry, Vol. 55, Issue 15 https://doi.org/10.1021/jo00302a007	journal	July 1990
Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010 Newman, David J.; Cragg, Gordon M. Journal of Natural Products, Vol. 75, Issue 3 https://doi.org/10.1021/np200906s	journal	January 2012
Why Are Secondary Metabolites (Natural Products) Biosynthesized? Williams, Dudley H.; Stone, Martin J.; Hauck, Peter R. Journal of Natural Products, Vol. 52, Issue 6 https://doi.org/10.1021/np50066a001	journal	November 1989
Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host Malpartida, F.; Hopwood, D. A. Nature, Vol. 309, Issue 5967 https://doi.org/10.1038/309462a0	journal	May 1984
Genome sequence of the endocellular bacterial symbiont of aphids Buchnera sp. APS Shigenobu, Shuji; Watanabe, Hidemi; Hattori, Masahira Nature, Vol. 407, Issue 6800 https://doi.org/10.1038/35024074	journal	September 2000
Genome evolution in bacterial endosymbionts of insects Wernegreen, Jennifer J. Nature Reviews Genetics, Vol. 3, Issue 11 https://doi.org/10.1038/nrg931	journal	November 2002
Extreme genome reduction in symbiotic bacteria McCutcheon, John P.; Moran, Nancy A. Nature Reviews Microbiology, Vol. 10, Issue 1 https://doi.org/10.1038/nrmicro2670	journal	November 2011
Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences Yarza, Pablo; Yilmaz, Pelin; Pruesse, Elmar Nature Reviews Microbiology, Vol. 12, Issue 9 https://doi.org/10.1038/nrmicro3330	journal	August 2014
Metabolites from symbiotic bacteria Piel, Jörn Nat. Prod. Rep., Vol. 26, Issue 3 https://doi.org/10.1039/B703499G	journal	January 2009
Development of Yondelis® (trabectedin, ET-743). A semisynthetic process solves the supply problem Cuevas, Carmen; Francesch, Andrés Natural Product Reports, Vol. 26, Issue 3 https://doi.org/10.1039/b808331m	journal	January 2009
Host cell-free growth of the Q fever bacterium Coxiella burnetii Omsland, A.; Cockrell, D. C.; Howe, D. Proceedings of the National Academy of Sciences, Vol. 106, Issue 11 https://doi.org/10.1073/pnas.0812074106	journal	February 2009
Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line Peng, C.; Pu, J. -Y.; Song, L. -Q. Proceedings of the National Academy of Sciences, Vol. 109, Issue 22 https://doi.org/10.1073/pnas.1204232109	journal	May 2012
Genome streamlining and chemical defense in a coral reef symbiosis Kwan, J. C.; Donia, M. S.; Han, A. W. Proceedings of the National Academy of Sciences, Vol. 109, Issue 50 https://doi.org/10.1073/pnas.1213820109	journal	November 2012
Accelerated evolution and Muller's rachet in endosymbiotic bacteria. Moran, N. A. Proceedings of the National Academy of Sciences, Vol. 93, Issue 7 https://doi.org/10.1073/pnas.93.7.2873	journal	April 1996
The Pyruvate Dehydrogenase Complexes: Structure-based Function and Regulation Patel, Mulchand S.; Nemeria, Natalia S.; Furey, William Journal of Biological Chemistry, Vol. 289, Issue 24 https://doi.org/10.1074/jbc.R114.563148	journal	May 2014
Deletional Bias across the Three Domains of Life Kuo, Chih-Horng; Ochman, Howard Genome Biology and Evolution, Vol. 1 https://doi.org/10.1093/gbe/evp016	journal	January 2009
Selfish Operons: Horizontal Transfer May Drive the Evolution of Gene Clusters Lawrence, Jeffrey G.; Roth, John R. Genetics, Vol. 143, Issue 4 https://doi.org/10.1093/genetics/143.4.1843	journal	August 1996
BAGEL3: automated identification of genes encoding bacteriocins and (non-)bactericidal posttranslationally modified peptides van Heel, Auke J.; de Jong, Anne; Montalbán-López, Manuel Nucleic Acids Research, Vol. 41, Issue W1 https://doi.org/10.1093/nar/gkt391	journal	May 2013
antiSMASH 2.0—a versatile platform for genome mining of secondary metabolite producers Blin, Kai; Medema, Marnix H.; Kazempour, Daniyal Nucleic Acids Research, Vol. 41, Issue W1 https://doi.org/10.1093/nar/gkt449	journal	May 2013
IMG/M 4 version of the integrated metagenome comparative analysis system Markowitz, Victor M.; Chen, I-Min A.; Chu, Ken Nucleic Acids Research, Vol. 42, Issue D1, p. D568-D573 https://doi.org/10.1093/nar/gkt919	journal	October 2013
IMG 4 version of the integrated microbial genomes comparative analysis system Markowitz, Victor M.; Chen, I-Min A.; Palaniappan, Krishna Nucleic Acids Research, Vol. 42, Issue D1 https://doi.org/10.1093/nar/gkt963	journal	October 2013
A new Myxococcus xanthus gene cluster for the biosynthesis of the antibiotic saframycin Mx1 encoding a peptide synthetase Pospiech, A.; Cluzel, B.; Bietenhader, J. Microbiology, Vol. 141, Issue 8 https://doi.org/10.1099/13500872-141-8-1793	journal	August 1995
The consequences of genetic drift for bacterial genome complexity Kuo, C. -H.; Moran, N. A.; Ochman, H. Genome Research, Vol. 19, Issue 8 https://doi.org/10.1101/gr.091785.109	journal	June 2009
Circos: An information aesthetic for comparative genomics Krzywinski, M.; Schein, J.; Birol, I. Genome Research, Vol. 19, Issue 9 https://doi.org/10.1101/gr.092759.109	journal	June 2009
Operon formation is driven by co-regulation and not by horizontal gene transfer Price, M. N. Genome Research, Vol. 15, Issue 6 https://doi.org/10.1101/gr.3368805	journal	May 2005
On the evolution of functional secondary metabolites (natural products) Stone, M. J.; Williams, D. H. Molecular Microbiology, Vol. 6, Issue 1 https://doi.org/10.1111/j.1365-2958.1992.tb00834.x	journal	January 1992
Molecular characterization of the safracin biosynthetic pathway from Pseudomonas fluorescens A2-2: designing new cytotoxic compounds: Safracin biosynthetic pathway Velasco, Ana; Acebo, Paloma; Gomez, Alicia Molecular Microbiology, Vol. 56, Issue 1 https://doi.org/10.1111/j.1365-2958.2004.04433.x	journal	February 2005
From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants: The emergence of metabolic gene clusters in plants Chu, Hoi Yee; Wegel, Eva; Osbourn, Anne The Plant Journal, Vol. 66, Issue 1 https://doi.org/10.1111/j.1365-313X.2011.04503.x	journal	March 2011
Carbon metabolism of intracellular bacteria Munoz-Elias, Ernesto J.; McKinney, John D. Cellular Microbiology, Vol. 8, Issue 1 https://doi.org/10.1111/j.1462-5822.2005.00648.x	journal	January 2006
Production of Ecteinascidia turbinata (Ascidiacea: Perophoridae) for Obtaining Anticancer Compounds Carballo, José Luis; Naranjo, Santiago; Kukurtzü, Bulent Journal of the World Aquaculture Society, Vol. 31, Issue 4 https://doi.org/10.1111/j.1749-7345.2000.tb00900.x	journal	December 2000
Toward Automatic Reconstruction of a Highly Resolved Tree of Life Ciccarelli, F. D. Science, Vol. 311, Issue 5765 https://doi.org/10.1126/science.1123061	journal	March 2006
A Small Microbial Genome: The End of a Long Symbiotic Relationship? Perez-Brocal, V.; Gil, R.; Ramos, S. Science, Vol. 314, Issue 5797 https://doi.org/10.1126/science.1130441	journal	October 2006
Characterization of the Saframycin A Gene Cluster from Streptomyces lavendulae NRRL 11002 Revealing a Nonribosomal Peptide Synthetase System for Assembling the Unusual Tetrapeptidyl Skeleton in an Iterative Manner Li, L.; Deng, W.; Song, J. Journal of Bacteriology, Vol. 190, Issue 1 https://doi.org/10.1128/JB.00826-07	journal	November 2007
Towards a Genome-Based Taxonomy for Prokaryotes Konstantinidis, K. T.; Tiedje, J. M. Journal of Bacteriology, Vol. 187, Issue 18 https://doi.org/10.1128/JB.187.18.6258-6264.2005	journal	September 2005
Genomics and Evolution of Heritable Bacterial Symbionts Moran, Nancy A.; McCutcheon, John P.; Nakabachi, Atsushi Annual Review of Genetics, Vol. 42, Issue 1 https://doi.org/10.1146/annurev.genet.41.110306.130119	journal	December 2008
Measurement of in Situ Activities of Nonphotosynthetic Microorganisms in Aquatic and Terrestrial Habitats Staley, J. T.; Konopka, A. Annual Review of Microbiology, Vol. 39, Issue 1 https://doi.org/10.1146/annurev.mi.39.100185.001541	journal	October 1985
Automated genome mining for natural products Li, Michael HT; Ung, Peter MU; Zajkowski, James BMC Bioinformatics, Vol. 10, Issue 1 https://doi.org/10.1186/1471-2105-10-185	journal	January 2009
Evolution of an endofungal Lifestyle: Deductions from the Burkholderia rhizoxinica Genome Lackner, Gerald; Moebius, Nadine; Partida-Martinez, Laila P. BMC Genomics, Vol. 12, Issue 1 https://doi.org/10.1186/1471-2164-12-210	journal	May 2011
Community-wide analysis of microbial genome sequence signatures Dick, Gregory J.; Andersson, Anders F.; Baker, Brett J. Genome Biology, Vol. 10, Issue 8 https://doi.org/10.1186/gb-2009-10-8-r85	journal	January 2009
Endosymbiotic Bacteria in Insects: Their Diversity and Culturability Kikuchi, Yoshitomo Microbes and Environments, Vol. 24, Issue 3 https://doi.org/10.1264/jsme2.ME09140S	journal	January 2009
Metabolic Complementarity and Genomics of the Dual Bacterial Symbiosis of Sharpshooters Wu, Dongying; Daugherty, Sean C.; Van Aken, Susan E. PLoS Biology, Vol. 4, Issue 6 https://doi.org/10.1371/journal.pbio.0040188	journal	June 2006
Bacterial Endosymbiosis in a Chordate Host: Long-Term Co-Evolution and Conservation of Secondary Metabolism Kwan, Jason C.; Schmidt, Eric W. PLoS ONE, Vol. 8, Issue 12 https://doi.org/10.1371/journal.pone.0080822	journal	December 2013
Host Control of Symbiont Natural Product Chemistry in Cryptic Populations of the Tunicate Lissoclinum patella Kwan, Jason C.; Tianero, Ma. Diarey B.; Donia, Mohamed S. PLoS ONE, Vol. 9, Issue 5 https://doi.org/10.1371/journal.pone.0095850	journal	May 2014
Defense of Ascidians and Their Conspicuous Larvae: Adult vs. Larval Chemical Defenses Lindquist, Niels; Hay, Mark E.; Fenical, William Ecological Monographs, Vol. 62, Issue 4 https://doi.org/10.2307/2937316	journal	February 1992
Ecteinascidia turbinata Extracts Inhibit DNA Synthesis in Lymphocytes After Mitogenic Stimulation by Lectins Lichter, W.; Lopez, D. M.; Wellham, L. L. Experimental Biology and Medicine, Vol. 150, Issue 2 https://doi.org/10.3181/00379727-150-39059	journal	November 1975
Evolution of an endofungal Lifestyle: Deductions from the Burkholderia rhizoxinica Genome Lackner, Gerald; Moebius, Nadine; Partida-Martinez, Laila P. figshare https://doi.org/10.6084/m9.figshare.c.4845360	collection	January 2021

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Title: Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743

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