Advanced tools in marine natural drug discovery.

Marine natural products (MNPs) remain promising drug sources with several marine-derived drugs having been successfully approved. Nevertheless, it is never a smooth sailing to seek bioactive compounds from marine environments, during which many challenges are need to be faced to, for example, discovering unique marine resources, reviving unculturable organisms outside the marine environment, distinguishing novel compounds from the known ones, and disclosing the function of MNPs and optimizing their pharmacological use. Herein we review some advanced techniques and methodologies that can be employed to deal with above challenges with the intent of inspiring the forthcoming efforts in MNPs discovery pipelines.

[1]  Sebastian Böcker,et al.  New kids on the block: novel informatics methods for natural product discovery. , 2014, Natural product reports.

[2]  E. Krausz,et al.  Cell-based high-content screening of small-molecule libraries. , 2007, Current opinion in chemical biology.

[3]  Pieter C. Dorrestein,et al.  A mass spectrometry-guided genome mining approach for natural product peptidogenomics , 2011, Nature chemical biology.

[4]  B. Moore,et al.  Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining. , 2015, ACS chemical biology.

[5]  John A. Tallarico,et al.  Integrating high-content screening and ligand-target prediction to identify mechanism of action. , 2008, Nature chemical biology.

[6]  Andrew W. Han,et al.  Genome streamlining and chemical defense in a coral reef symbiosis , 2012, Proceedings of the National Academy of Sciences.

[7]  Shu‐Ming Li,et al.  Acetylaszonalenin Biosynthesis in Neosartorya fischeri , 2009, Journal of Biological Chemistry.

[8]  H. Vlamakis,et al.  Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis , 2015, Scientific Reports.

[9]  O. Potterat,et al.  Liquid chromatography-electrospray time-of-flight mass spectrometry for on-line accurate mass determination and identification of cyclodepsipeptides in a crude extract of the fungus Metarrhizium anisopliae. , 2000, Journal of chromatography. A.

[10]  Gregory L Challis,et al.  Mining microbial genomes for new natural products and biosynthetic pathways. , 2008, Microbiology.

[11]  Daniel W. Udwary,et al.  Significant Natural Product Biosynthetic Potential of Actinorhizal Symbionts of the Genus Frankia, as Revealed by Comparative Genomic and Proteomic Analyses , 2011, Applied and Environmental Microbiology.

[12]  Jian Wang,et al.  High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections , 2007, Proceedings of the National Academy of Sciences.

[13]  Markiyan Samborskyy,et al.  Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338 , 2007, Nature Biotechnology.

[14]  Antony J Williams,et al.  Structural revisions of natural products by Computer-Assisted Structure Elucidation (CASE) systems. , 2010, Natural product reports.

[15]  Lei Fang,et al.  Tailoring pathway modularity in the biosynthesis of erythromycin analogs heterologously engineered in E. coli , 2015, Science Advances.

[16]  D. Sherman,et al.  Identification and analysis of the bacterial endosymbiont specialized for production of the chemotherapeutic natural product ET-743. , 2015, Environmental microbiology.

[17]  Hartmut Laatsch,et al.  Evolving trends in the dereplication of natural product extracts: new methodology for rapid, small-scale investigation of natural product extracts. , 2008, Journal of natural products.

[18]  Huimin Zhao,et al.  New tools for reconstruction and heterologous expression of natural product biosynthetic gene clusters. , 2016, Natural product reports.

[19]  Yeo Joon Yoon,et al.  Reinvigorating natural product combinatorial biosynthesis with synthetic biology. , 2015, Nature chemical biology.

[20]  S. Brady,et al.  Metagenomic approaches to natural products from free-living and symbiotic organisms. , 2009, Natural product reports.

[21]  Wenjun Jiang,et al.  Cas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters , 2015, Nature Communications.

[22]  P. Dorrestein,et al.  Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A , 2014, Proceedings of the National Academy of Sciences.

[23]  Giuseppe Testa,et al.  DNA cloning by homologous recombination in Escherichia coli , 2000, Nature Biotechnology.

[24]  Wei Xu,et al.  Epigenetic genome mining of an endophytic fungus leads to the pleiotropic biosynthesis of natural products. , 2015, Angewandte Chemie.

[25]  Huimin Zhao,et al.  DNA assembler: a synthetic biology tool for characterizing and engineering natural product gene clusters. , 2012, Methods in enzymology.

[26]  Wolfgang Link,et al.  High content screening: seeing is believing. , 2010, Trends in biotechnology.

[27]  Roger G. Linington,et al.  Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters , 2014, Cell.

[28]  Huimin Zhao,et al.  Direct cloning of large genomic sequences , 2012, Nature Biotechnology.

[29]  H. Gaspar,et al.  Marketed Marine Natural Products in the Pharmaceutical and Cosmeceutical Industries: Tips for Success , 2014, Marine drugs.

[30]  David C. Smith,et al.  Targeted search for actinomycetes from nearshore and deep-sea marine sediments. , 2013, FEMS microbiology ecology.

[31]  Nuno Bandeira,et al.  Automated Genome Mining of Ribosomal Peptide Natural Products , 2014, ACS chemical biology.

[32]  Robert J. Feeney,et al.  CONTRIBUTIONS TO THE STUDY OF MARINE PRODUCTS. XXXII. THE NUCLEOSIDES OF SPONGES. I.1 , 1951 .

[33]  D. Bojanic,et al.  Impact of high-throughput screening in biomedical research , 2011, Nature Reviews Drug Discovery.

[34]  Zengyou He,et al.  Technical, bioinformatical and statistical aspects of liquid chromatography-mass spectrometry (LC-MS) and capillary electrophoresis-mass spectrometry (CE-MS) based clinical proteomics: a critical assessment. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[35]  Natalia N. Ivanova,et al.  Insights into the phylogeny and coding potential of microbial dark matter , 2013, Nature.

[36]  Joshua M. Stuart,et al.  "Function-first" lead discovery: mode of action profiling of natural product libraries using image-based screening. , 2013, Chemistry & biology.

[37]  Peter J. Smith,et al.  Identification of major and minor constituents of Harpagophytum procumbens (Devil's claw) using HPLC-SPE-NMR and HPLC-ESIMS/APCIMS. , 2006, Journal of natural products.

[38]  Roger G Linington,et al.  Integration of high-content screening and untargeted metabolomics for comprehensive functional annotation of natural product libraries , 2015, Proceedings of the National Academy of Sciences.

[39]  Jay D Keasling,et al.  Engineering Escherichia coli for production of functionalized terpenoids using plant P450s. , 2007, Nature chemical biology.

[40]  T. Molinski,et al.  Drug development from marine natural products , 2009, Nature Reviews Drug Discovery.

[41]  K. Sivonen,et al.  Genome Mining Demonstrates the Widespread Occurrence of Gene Clusters Encoding Bacteriocins in Cyanobacteria , 2011, PloS one.

[42]  Blaine A. Pfeifer,et al.  Biosynthesis of Polyketides in Heterologous Hosts , 2001, Microbiology and Molecular Biology Reviews.

[43]  R. Daniel,et al.  Achievements and new knowledge unraveled by metagenomic approaches , 2009, Applied Microbiology and Biotechnology.

[44]  Q. Cui,et al.  Cloning, Characterization and Heterologous Expression of the Indolocarbazole Biosynthetic Gene Cluster from Marine-Derived Streptomyces sanyensis FMA , 2013, Marine drugs.

[45]  B A Pfeifer,et al.  Biosynthesis of Complex Polyketides in a Metabolically Engineered Strain of E. coli , 2001, Science.

[46]  Keith E. J. Tyo,et al.  Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli , 2010, Science.

[47]  H. Yeh,et al.  Biosynthetic pathway for the epipolythiodioxopiperazine acetylaranotin in Aspergillus terreus revealed by genome-based deletion analysis. , 2013, Journal of the American Chemical Society.

[48]  Kenneth A. Miller,et al.  Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine-derived Aspergillus sp. , 2010, Journal of the American Chemical Society.

[49]  Hong-Yu Zhang,et al.  Marine natural products as sources of novel scaffolds: achievement and concern. , 2010, Drug discovery today.

[50]  D. G. Gibson,et al.  Enzymatic assembly of DNA molecules up to several hundred kilobases , 2009, Nature Methods.

[51]  B. Pfeifer,et al.  Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host. , 2010, Chemistry & biology.

[52]  Roger G. Linington,et al.  Molecular networking as a dereplication strategy. , 2013, Journal of natural products.

[53]  G. Aleti,et al.  Genome mining: Prediction of lipopeptides and polyketides from Bacillus and related Firmicutes , 2015, Computational and structural biotechnology journal.

[54]  Haoran Zhang,et al.  Methods and options for the heterologous production of complex natural products. , 2011, Natural product reports.

[55]  G. Challis,et al.  Strategies for the Discovery of New Natural Products by Genome Mining , 2009, Chembiochem : a European journal of chemical biology.

[56]  C. Jiménez,et al.  NMR methods for unravelling the spectra of complex mixtures. , 2011, Natural product reports.

[57]  Christopher N. Boddy,et al.  Bioinformatics tools for genome mining of polyketide and non-ribosomal peptides , 2014, Journal of Industrial Microbiology & Biotechnology.

[58]  Susana P. Gaudêncio,et al.  Dereplication: racing to speed up the natural products discovery process. , 2015, Natural product reports.

[59]  A. Harvey,et al.  The re-emergence of natural products for drug discovery in the genomics era , 2015, Nature Reviews Drug Discovery.

[60]  Young Ji Yoo,et al.  Heterologous production of 4-O-demethylbarbamide, a marine cyanobacterial natural product. , 2012, Organic letters.

[61]  Paula Y. Calle,et al.  Mapping gene clusters within arrayed metagenomic libraries to expand the structural diversity of biomedically relevant natural products , 2013, Proceedings of the National Academy of Sciences.

[62]  Hui Guo,et al.  Bioprospecting for antituberculosis leads from microbial metabolites. , 2010, Natural product reports.

[63]  Carola Engler,et al.  Golden Gate Shuffling: A One-Pot DNA Shuffling Method Based on Type IIs Restriction Enzymes , 2009, PloS one.

[64]  Micheal C. Wilson,et al.  The Discovery of Salinosporamide K from the Marine Bacterium “Salinispora pacifica” by Genome Mining Gives Insight into Pathway Evolution , 2011, Chembiochem : a European journal of chemical biology.

[65]  Christian Rinke,et al.  An environmental bacterial taxon with a large and distinct metabolic repertoire , 2014, Nature.

[66]  Y. Chooi,et al.  Elucidation of the concise biosynthetic pathway of the communesin indole alkaloids. , 2015, Angewandte Chemie.

[67]  R. Müller,et al.  Secondary metabolomics: the impact of mass spectrometry-based approaches on the discovery and characterization of microbial natural products. , 2014, Natural product reports.

[68]  Yaoquan Liu,et al.  Heterologous production of epothilone C and D in Escherichia coli. , 2006, Biochemistry.

[69]  M. Donia,et al.  Accessing the Hidden Majority of Marine Natural Products through Metagenomics , 2011, Chembiochem : a European journal of chemical biology.

[70]  B. Moore,et al.  Direct Capture and Heterologous Expression of Salinispora Natural Product Genes for the Biosynthesis of Enterocin , 2014, Journal of natural products.

[71]  K. Nielsen,et al.  The importance of mass spectrometric dereplication in fungal secondary metabolite analysis , 2015, Front. Microbiol..

[72]  W. A. van der Donk,et al.  Genome mining for ribosomally synthesized natural products. , 2011, Current opinion in chemical biology.

[73]  P. Glatzel,et al.  SUPPORTING INFORMATION , 2003 .

[74]  P. Jensen,et al.  Hybrid isoprenoid secondary metabolite production in terrestrial and marine actinomycetes. , 2010, Current opinion in biotechnology.