Streptomyces and Saccharopolyspora Hosts for Heterologous Expression of Secondary Metabolite Gene Clusters

Overview

Journal J Ind Microbiol Biotechnol

Publisher Oxford University Press

Specialty Biotechnology

Date 2010 May 15

PMID 20467781

Citations 86

Authors

Richard H Baltz

Affiliations

Soon will be listed here.

Abstract

Natural products discovery from actinomycetes has been on the decline in recent years, and has suffered from a lack of innovative ways to discover new secondary metabolites within a background of the thousands of known compounds. Recent advances in whole genome sequencing have revealed that actinomycetes with large genomes encode multiple secondary metabolite pathways, most of which remain cryptic. One approach to address the expression of cryptic pathways is to first identify novel pathways by bioinformatics, then clone and express them in well-characterized hosts with known secondary metabolomes. This process should eliminate the tedious dereplication process that has hampered natural products discovery. Several laboratory and industrial production strains have been used for heterologous production of secondary metabolite pathways. This review discusses the results of these studies, and the pros and cons of using various Streptomyces and one Saccharopolyspora strain for heterologous expression. This information should provide an experimental basis to help researchers choose hosts for current application and future development to express heterologous secondary metabolite pathways in yields sufficient for rapid scale-up, biological testing, and commercial production.

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References

Matsushima P, Baltz R . A gene cloning system for 'Streptomyces toyocaensis'. Microbiology (Reading). 1996; 142 ( Pt 2):261-267. DOI: 10.1099/13500872-142-2-261. View

Binnie C, Warren M, Butler M . Cloning and heterologous expression in Streptomyces lividans of Streptomyces rimosus genes involved in oxytetracycline biosynthesis. J Bacteriol. 1989; 171(2):887-95. PMC: 209679. DOI: 10.1128/jb.171.2.887-895.1989. View

Tetzlaff C, You Z, Cane D, Takamatsu S, Omura S, Ikeda H . A gene cluster for biosynthesis of the sesquiterpenoid antibiotic pentalenolactone in Streptomyces avermitilis. Biochemistry. 2006; 45(19):6179-86. PMC: 2518623. DOI: 10.1021/bi060419n. View

Bibb M, Hesketh A . Chapter 4. Analyzing the regulation of antibiotic production in streptomycetes. Methods Enzymol. 2009; 458:93-116. DOI: 10.1016/S0076-6879(09)04804-6. View

Epp J, Burgett S, Schoner B . Cloning and nucleotide sequence of a carbomycin-resistance gene from Streptomyces thermotolerans. Gene. 1987; 53(1):73-83. DOI: 10.1016/0378-1119(87)90094-1. View

Van Lanen S, Shen B . Microbial genomics for the improvement of natural product discovery. Curr Opin Microbiol. 2006; 9(3):252-60. DOI: 10.1016/j.mib.2006.04.002. View

Eustaquio A, Gust B, Galm U, Li S, Chater K, Heide L . Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters. Appl Environ Microbiol. 2005; 71(5):2452-9. PMC: 1087579. DOI: 10.1128/AEM.71.5.2452-2459.2005. View

McHenney M, Baltz R . Transposition of Tn5096 from a temperature-sensitive transducible plasmid in Streptomyces spp. J Bacteriol. 1991; 173(17):5578-81. PMC: 208276. DOI: 10.1128/jb.173.17.5578-5581.1991. View

Epp J, Huber M, Turner J, Goodson T, Schoner B . Production of a hybrid macrolide antibiotic in Streptomyces ambofaciens and Streptomyces lividans by introduction of a cloned carbomycin biosynthetic gene from Streptomyces thermotolerans. Gene. 1989; 85(2):293-301. DOI: 10.1016/0378-1119(89)90421-6. View

10.

Hosted T, Baltz R . Use of rpsL for dominance selection and gene replacement in Streptomyces roseosporus. J Bacteriol. 1997; 179(1):180-6. PMC: 178677. DOI: 10.1128/jb.179.1.180-186.1997. View

11.

Nett M, Ikeda H, Moore B . Genomic basis for natural product biosynthetic diversity in the actinomycetes. Nat Prod Rep. 2009; 26(11):1362-84. PMC: 3063060. DOI: 10.1039/b817069j. View

12.

Kuhstoss S, Richardson M, Rao R . Site-specific integration in Streptomyces ambofaciens: localization of integration functions in S. ambofaciens plasmid pSAM2. J Bacteriol. 1989; 171(1):16-23. PMC: 209547. DOI: 10.1128/jb.171.1.16-23.1989. View

13.

Kwon H, Smith W, Xiang L, Shen B . Cloning and heterologous expression of the macrotetrolide biosynthetic gene cluster revealed a novel polyketide synthase that lacks an acyl carrier protein. J Am Chem Soc. 2001; 123(14):3385-6. DOI: 10.1021/ja0100827. View

14.

Rodriguez A, Olano C, Vilches C, Mendez C, Salas J . Streptomyces antibioticus contains at least three oleandomycin-resistance determinants, one of which shows similarity with proteins of the ABC-transporter superfamily. Mol Microbiol. 1993; 8(3):571-82. DOI: 10.1111/j.1365-2958.1993.tb01601.x. View

15.

Baltz R . Marcel Faber Roundtable: is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration?. J Ind Microbiol Biotechnol. 2006; 33(7):507-13. DOI: 10.1007/s10295-005-0077-9. View

16.

Alexander D, Rock J, He X, Brian P, Miao V, Baltz R . Development of a genetic system for combinatorial biosynthesis of lipopeptides in Streptomyces fradiae and heterologous expression of the A54145 biosynthesis gene cluster. Appl Environ Microbiol. 2010; 76(20):6877-87. PMC: 2953024. DOI: 10.1128/AEM.01248-10. View

17.

Galm U, Shen B . Expression of biosynthetic gene clusters in heterologous hosts for natural product production and combinatorial biosynthesis. Expert Opin Drug Discov. 2013; 1(5):409-37. DOI: 10.1517/17460441.1.5.409. View

18.

Corre C, Challis G . New natural product biosynthetic chemistry discovered by genome mining. Nat Prod Rep. 2009; 26(8):977-86. DOI: 10.1039/b713024b. View

19.

Kuhstoss S, Huber M, Turner J, Paschal J, Rao R . Production of a novel polyketide through the construction of a hybrid polyketide synthase. Gene. 1996; 183(1-2):231-6. DOI: 10.1016/s0378-1119(96)00565-3. View

20.

Kim M, Ha H, Choi S . Conjugal transfer using the bacteriophage phiC31 att/int system and properties of the attB site in Streptomyces ambofaciens. Biotechnol Lett. 2007; 30(4):695-9. DOI: 10.1007/s10529-007-9586-0. View