Natural Product Discovery from the Human Microbiome

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2017 Apr 9

PMID 28389564

Citations 30

Authors

Matthew R Wilson

Li Zha

Emily P Balskus

Affiliations

Soon will be listed here.

Abstract

Human-associated microorganisms have the potential to biosynthesize numerous secondary metabolites that may mediate important host-microbe and microbe-microbe interactions. However, there is currently a limited understanding of microbiome-derived natural products. A variety of complementary discovery approaches have begun to illuminate this microbial "dark matter," which will in turn allow detailed mechanistic studies of the effects of these molecules on microbiome and host. Herein, we review recent efforts to uncover microbiome-derived natural products, describe the key approaches that were used to identify and characterize these metabolites, discuss potential functional roles of these molecules, and highlight challenges related to this emerging research area.

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References

Wang G, Graziani E, Waters B, Pan W, Li X, McDermott J . Novel natural products from soil DNA libraries in a streptomycete host. Org Lett. 2000; 2(16):2401-4. DOI: 10.1021/ol005860z. View

Brady S, Wagenaar M, Singh M, Janso J, Clardy J . The cytosporones, new octaketide antibiotics isolated from an endophytic fungus. Org Lett. 2000; 2(25):4043-6. DOI: 10.1021/ol006680s. View

Le L, Kabarowski J, Weng Z, Satterthwaite A, Harvill E, Jensen E . Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome. Immunity. 2001; 14(5):561-71. DOI: 10.1016/s1074-7613(01)00145-5. View

Wolkenberg S, Boger D . Mechanisms of in situ activation for DNA-targeting antitumor agents. Chem Rev. 2002; 102(7):2477-95. DOI: 10.1021/cr010046q. View

Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez de Fonseca F . Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature. 2003; 425(6953):90-3. DOI: 10.1038/nature01921. View

Berdy J . Bioactive microbial metabolites. J Antibiot (Tokyo). 2005; 58(1):1-26. DOI: 10.1038/ja.2005.1. View

Brady S, Clardy J . Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew Chem Int Ed Engl. 2005; 44(43):7063-5. DOI: 10.1002/anie.200501941. View

Nougayrede J, Homburg S, Taieb F, Boury M, Brzuszkiewicz E, Gottschalk G . Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science. 2006; 313(5788):848-51. DOI: 10.1126/science.1127059. View

Rimmerman N, Bradshaw H, Hughes H, Chen J, Hu S, McHugh D . N-palmitoyl glycine, a novel endogenous lipid that acts as a modulator of calcium influx and nitric oxide production in sensory neurons. Mol Pharmacol. 2008; 74(1):213-24. PMC: 8130248. DOI: 10.1124/mol.108.045997. View

10.

Sattely E, Fischbach M, Walsh C . Total biosynthesis: in vitro reconstitution of polyketide and nonribosomal peptide pathways. Nat Prod Rep. 2008; 25(4):757-93. DOI: 10.1039/b801747f. View

11.

Wieland Brown L, Acker M, Clardy J, Walsh C, Fischbach M . Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin. Proc Natl Acad Sci U S A. 2009; 106(8):2549-53. PMC: 2650375. DOI: 10.1073/pnas.0900008106. View

12.

Piel J . Metabolites from symbiotic bacteria. Nat Prod Rep. 2009; 26(3):338-62. DOI: 10.1039/b703499g. View

13.

Brady S, Simmons L, Kim J, Schmidt E . Metagenomic approaches to natural products from free-living and symbiotic organisms. Nat Prod Rep. 2009; 26(11):1488-503. PMC: 2919151. DOI: 10.1039/b817078a. View

14.

Lewis K, Epstein S, Donofrio A, Ling L . Uncultured microorganisms as a source of secondary metabolites. J Antibiot (Tokyo). 2010; 63(8):468-76. DOI: 10.1038/ja.2010.87. View

15.

Yang J, Karr J, Watrous J, Dorrestein P . Integrating '-omics' and natural product discovery platforms to investigate metabolic exchange in microbiomes. Curr Opin Chem Biol. 2010; 15(1):79-87. PMC: 3174688. DOI: 10.1016/j.cbpa.2010.10.025. View

16.

Tlaskalova-Hogenova H, Stepankova R, Kozakova H, Hudcovic T, Vannucci L, Tuckova L . The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol. 2011; 8(2):110-20. PMC: 4003137. DOI: 10.1038/cmi.2010.67. View

17.

Grice E, Segre J . The skin microbiome. Nat Rev Microbiol. 2011; 9(4):244-53. PMC: 3535073. DOI: 10.1038/nrmicro2537. View

18.

Crawford J, Clardy J . Bacterial symbionts and natural products. Chem Commun (Camb). 2011; 47(27):7559-66. PMC: 3174269. DOI: 10.1039/c1cc11574j. View

19.

Dubois D, Baron O, Cougnoux A, Delmas J, Pradel N, Boury M . ClbP is a prototype of a peptidase subgroup involved in biosynthesis of nonribosomal peptides. J Biol Chem. 2011; 286(41):35562-35570. PMC: 3195562. DOI: 10.1074/jbc.M111.221960. View

20.

Reshef D, Reshef Y, Finucane H, Grossman S, McVean G, Turnbaugh P . Detecting novel associations in large data sets. Science. 2011; 334(6062):1518-24. PMC: 3325791. DOI: 10.1126/science.1205438. View