Actinomycetes Biosynthetic Potential: How to Bridge in Silico and in Vivo?

Overview

Journal J Ind Microbiol Biotechnol

Publisher Oxford University Press

Specialty Biotechnology

Date 2013 Oct 16

PMID 24127068

Citations 29

Authors

Yuriy Rebets

Elke Brotz

Bogdan Tokovenko

Andriy Luzhetskyy

Affiliations

Soon will be listed here.

Abstract

Actinomycetes genome sequencing and bioinformatic analyses revealed a large number of "cryptic" gene clusters coding for secondary metabolism. These gene clusters have the potential to increase the chemical diversity of natural products. Indeed, reexamination of well-characterized actinomycetes strains revealed a variety of hidden treasures. Growing information about this metabolic diversity has promoted further development of strategies to discover novel biologically active compounds produced by actinomycetes. This new task for actinomycetes genetics requires the development and use of new approaches and tools. Application of synthetic biology approaches led to the development of a set of strategies and tools to satisfy these new requirements. In this review, we discuss strategies and methods to discover small molecules produced by these fascinating bacteria and also discuss a variety of genetic instruments and regulatory elements used to activate secondary metabolism cryptic genes for the overproduction of these metabolites.

Citing Articles

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Bacteria as genetically programmable producers of bioactive natural products.

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A visualization reporter system for characterizing antibiotic biosynthetic gene clusters expression with high-sensitivity.

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References

Schmitt-John T, Engels J . Promoter constructions for efficient secretion expression in Streptomyces lividans. Appl Microbiol Biotechnol. 1992; 36(4):493-8. DOI: 10.1007/BF00170190. View

Boddy C, Hotta K, Tse M, Watts R, Khosla C . Precursor-directed biosynthesis of epothilone in Escherichia coli. J Am Chem Soc. 2004; 126(24):7436-7. DOI: 10.1021/ja048108s. View

DeSanti C, Strohl W . Characterization of the Streptomyces sp. strain C5 snp locus and development of snp-derived expression vectors. Appl Environ Microbiol. 2003; 69(3):1647-54. PMC: 150044. DOI: 10.1128/AEM.69.3.1647-1654.2003. View

Bibb M, Janssen G, Ward J . Cloning and analysis of the promoter region of the erythromycin resistance gene (ermE) of Streptomyces erythraeus. Gene. 1985; 38(1-3):215-26. DOI: 10.1016/0378-1119(85)90220-3. View

Yague P, Rodriguez-Garcia A, Lopez-Garcia M, Martin J, Rioseras B, Sanchez J . Transcriptomic analysis of Streptomyces coelicolor differentiation in solid sporulating cultures: first compartmentalized and second multinucleated mycelia have different and distinctive transcriptomes. PLoS One. 2013; 8(3):e60665. PMC: 3610822. DOI: 10.1371/journal.pone.0060665. View

Nguyen K, Au-Young S, Nodwell J . Monomeric red fluorescent protein as a reporter for macromolecular localization in Streptomyces coelicolor. Plasmid. 2007; 58(2):167-73. DOI: 10.1016/j.plasmid.2007.03.005. View

Zhou M, Jing X, Xie P, Chen W, Wang T, Xia H . Sequential deletion of all the polyketide synthase and nonribosomal peptide synthetase biosynthetic gene clusters and a 900-kb subtelomeric sequence of the linear chromosome of Streptomyces coelicolor. FEMS Microbiol Lett. 2012; 333(2):169-79. DOI: 10.1111/j.1574-6968.2012.02609.x. View

Khodakaramian G, Lissenden S, Gust B, Moir L, Hoskisson P, Chater K . Expression of Cre recombinase during transient phage infection permits efficient marker removal in Streptomyces. Nucleic Acids Res. 2006; 34(3):e20. PMC: 1363781. DOI: 10.1093/nar/gnj019. View

Blin K, Medema M, Kazempour D, Fischbach M, Breitling R, Takano E . antiSMASH 2.0--a versatile platform for genome mining of secondary metabolite producers. Nucleic Acids Res. 2013; 41(Web Server issue):W204-12. PMC: 3692088. DOI: 10.1093/nar/gkt449. View

10.

Gottelt M, Kol S, Gomez-Escribano J, Bibb M, Takano E . Deletion of a regulatory gene within the cpk gene cluster reveals novel antibacterial activity in Streptomyces coelicolor A3(2). Microbiology (Reading). 2010; 156(Pt 8):2343-2353. DOI: 10.1099/mic.0.038281-0. View

11.

Laureti L, Song L, Huang S, Corre C, Leblond P, Challis G . Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens. Proc Natl Acad Sci U S A. 2011; 108(15):6258-63. PMC: 3076887. DOI: 10.1073/pnas.1019077108. View

12.

Romby P, Charpentier E . An overview of RNAs with regulatory functions in gram-positive bacteria. Cell Mol Life Sci. 2009; 67(2):217-37. PMC: 11115938. DOI: 10.1007/s00018-009-0162-8. View

13.

Deng Z, Kieser T, Hopwood D . Activity of a Streptomyces transcriptional terminator in Escherichia coli. Nucleic Acids Res. 1987; 15(6):2665-75. PMC: 340676. DOI: 10.1093/nar/15.6.2665. View

14.

Willemse J, van Wezel G . Imaging of Streptomyces coelicolor A3(2) with reduced autofluorescence reveals a novel stage of FtsZ localization. PLoS One. 2009; 4(1):e4242. PMC: 2625393. DOI: 10.1371/journal.pone.0004242. View

15.

Takano H, Obitsu S, Beppu T, Ueda K . Light-induced carotenogenesis in Streptomyces coelicolor A3(2): identification of an extracytoplasmic function sigma factor that directs photodependent transcription of the carotenoid biosynthesis gene cluster. J Bacteriol. 2005; 187(5):1825-32. PMC: 1064024. DOI: 10.1128/JB.187.5.1825-1832.2005. View

16.

Ali N, Herron P, Evans M, Dyson P . Osmotic regulation of the Streptomyces lividans thiostrepton-inducible promoter, ptipA. Microbiology (Reading). 2002; 148(Pt 2):381-390. DOI: 10.1099/00221287-148-2-381. View

17.

Scholtissek S, Grosse F . A cloning cartridge of lambda t(o) terminator. Nucleic Acids Res. 1987; 15(7):3185. PMC: 340926. DOI: 10.1093/nar/15.7.3185. View

18.

Horinouchi S, Beppu T . Construction and application of a promoter-probe plasmid that allows chromogenic identification in Streptomyces lividans. J Bacteriol. 1985; 162(1):406-12. PMC: 219003. DOI: 10.1128/jb.162.1.406-412.1985. View

19.

Barona-Gomez F, Wong U, Giannakopulos A, Derrick P, Challis G . Identification of a cluster of genes that directs desferrioxamine biosynthesis in Streptomyces coelicolor M145. J Am Chem Soc. 2004; 126(50):16282-3. DOI: 10.1021/ja045774k. View

20.

Rudd B, Hopwood D . A pigmented mycelial antibiotic in Streptomyces coelicolor: control by a chromosomal gene cluster. J Gen Microbiol. 1980; 119(2):333-40. DOI: 10.1099/00221287-119-2-333. View