Genome Mining of the Streptomyces Avermitilis Genome and Development of Genome-minimized Hosts for Heterologous Expression of Biosynthetic Gene Clusters

Overview

Journal J Ind Microbiol Biotechnol

Publisher Oxford University Press

Specialty Biotechnology

Date 2013 Aug 31

PMID 23990133

Citations 77

Authors

Haruo Ikeda

Shin-ya Kazuo

Satoshi Omura

Affiliations

Soon will be listed here.

Abstract

To date, several actinomycete genomes have been completed and annotated. Among them, Streptomyces microorganisms are of major pharmaceutical interest because they are a rich source of numerous secondary metabolites. S. avermitilis is an industrial microorganism used for the production of an anthelmintic agent, avermectin, which is a commercially important antiparasitic agent in human and veterinary medicine, and agricultural pesticides. Genome analysis of S. avermitilis provides significant information for not only industrial applications but also understanding the features of this genus. On genome mining of S. avermitilis, the microorganism has been found to harbor at least 38 secondary metabolic gene clusters and 46 insertion sequence (IS)-like sequences on the genome, which have not been searched so far. A significant use of the genome data of Streptomyces microorganisms is the construction of a versatile host for heterologous expression of exogenous biosynthetic gene clusters by genetic engineering. Since S. avermitilis is used as an industrial microorganism, the microorganism is already optimized for the efficient supply of primary metabolic precursors and biochemical energy to support multistep biosynthesis. The feasibility of large-deletion mutants of S. avermitilis has been confirmed by heterologous expression of more than 20 exogenous biosynthetic gene clusters.

Citing Articles

Chemical biology research in RIKEN NPDepo aimed at agricultural applications.

Osada H Proc Jpn Acad Ser B Phys Biol Sci. 2025; 101(1):8-31.

PMID: 39805590 PMC: 11808203. DOI: 10.2183/pjab.101.003.

Fine-Tuning Genetic Circuits via Host Context and RBS Modulation.

Chan D, Winter L, Bjerg J, Krsmanovic S, Baldwin G, Bernstein H ACS Synth Biol. 2025; 14(1):193-205.

PMID: 39754601 PMC: 11744933. DOI: 10.1021/acssynbio.4c00551.

A metabologenomics strategy for rapid discovery of polyketides derived from modular polyketide synthases.

Liu R, Zhang Z, Li M, Zhang L Chem Sci. 2024; 16(4):1696-1706.

PMID: 39568943 PMC: 11575545. DOI: 10.1039/d4sc04174g.

Activation of Secondary Metabolism and Protease Activity Mechanisms in the Black Koji Mold through Coculture with Animal Cells.

Asano Y, Saito S, Ujie Y, Iwata C, Yaguchi T, Arai M ACS Omega. 2024; 9(42):43129-43137.

PMID: 39464474 PMC: 11500138. DOI: 10.1021/acsomega.4c07124.

Bioactive Compounds Produced by Endophytic Bacteria and Their Plant Hosts-An Insight into the World of Chosen Herbaceous Ruderal Plants in Central Europe.

Drozdzynski P, Rutkowska N, Rodziewicz M, Marchut-Mikolajczyk O Molecules. 2024; 29(18).

PMID: 39339451 PMC: 11433698. DOI: 10.3390/molecules29184456.

References

Lamb D, Ikeda H, Nelson D, Ishikawa J, Skaug T, Jackson C . Cytochrome p450 complement (CYPome) of the avermectin-producer Streptomyces avermitilis and comparison to that of Streptomyces coelicolor A3(2). Biochem Biophys Res Commun. 2003; 307(3):610-9. DOI: 10.1016/s0006-291x(03)01231-2. View

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

Ikeda H, Takada Y, Pang C, Tanaka H, Omura S . Transposon mutagenesis by Tn4560 and applications with avermectin-producing Streptomyces avermitilis. J Bacteriol. 1993; 175(7):2077-82. PMC: 204307. DOI: 10.1128/jb.175.7.2077-2082.1993. View

You Z, Omura S, Ikeda H, Cane D, Jogl G . Crystal structure of the non-heme iron dioxygenase PtlH in pentalenolactone biosynthesis. J Biol Chem. 2007; 282(50):36552-60. PMC: 3010413. DOI: 10.1074/jbc.M706358200. View

Medema M, Trefzer A, Kovalchuk A, van den Berg M, Muller U, Heijne W . The sequence of a 1.8-mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways. Genome Biol Evol. 2010; 2:212-24. PMC: 2997539. DOI: 10.1093/gbe/evq013. View

Solenberg P, Burgett S . Method for selection of transposable DNA and characterization of a new insertion sequence, IS493, from Streptomyces lividans. J Bacteriol. 1989; 171(9):4807-13. PMC: 210283. DOI: 10.1128/jb.171.9.4807-4813.1989. View

You Z, Omura S, Ikeda H, Cane D . Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlH, a non-heme iron dioxygenase of Streptomyces avermitilis. J Am Chem Soc. 2006; 128(20):6566-7. PMC: 2533727. DOI: 10.1021/ja061469i. View

Komatsu M, Uchiyama T, Omura S, Cane D, Ikeda H . Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism. Proc Natl Acad Sci U S A. 2010; 107(6):2646-51. PMC: 2823899. DOI: 10.1073/pnas.0914833107. View

Bignell D, Seipke R, Huguet-Tapia J, Chambers A, Parry R, Loria R . Streptomyces scabies 87-22 contains a coronafacic acid-like biosynthetic cluster that contributes to plant-microbe interactions. Mol Plant Microbe Interact. 2010; 23(2):161-75. DOI: 10.1094/MPMI-23-2-0161. View

10.

Komatsu M, Komatsu K, Koiwai H, Yamada Y, Kozone I, Izumikawa M . Engineered Streptomyces avermitilis host for heterologous expression of biosynthetic gene cluster for secondary metabolites. ACS Synth Biol. 2013; 2(7):384-96. PMC: 3932656. DOI: 10.1021/sb3001003. View

11.

Lautru S, Deeth R, Bailey L, Challis G . Discovery of a new peptide natural product by Streptomyces coelicolor genome mining. Nat Chem Biol. 2006; 1(5):265-9. DOI: 10.1038/nchembio731. View

12.

Ikeda H, Nonomiya T, Usami M, Ohta T, Omura S . Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis. Proc Natl Acad Sci U S A. 1999; 96(17):9509-14. PMC: 22239. DOI: 10.1073/pnas.96.17.9509. View

13.

Komatsu M, Tsuda M, Omura S, Oikawa H, Ikeda H . Identification and functional analysis of genes controlling biosynthesis of 2-methylisoborneol. Proc Natl Acad Sci U S A. 2008; 105(21):7422-7. PMC: 2387273. DOI: 10.1073/pnas.0802312105. View

14.

Pullan S, Chandra G, Bibb M, Merrick M . Genome-wide analysis of the role of GlnR in Streptomyces venezuelae provides new insights into global nitrogen regulation in actinomycetes. BMC Genomics. 2011; 12:175. PMC: 3087709. DOI: 10.1186/1471-2164-12-175. View

15.

Feng Z, Wang L, Rajski S, Xu Z, Coeffet-LeGal M, Shen B . Engineered production of iso-migrastatin in heterologous Streptomyces hosts. Bioorg Med Chem. 2008; 17(6):2147-53. PMC: 3075207. DOI: 10.1016/j.bmc.2008.10.074. View

16.

Wang X, Yan Y, Zhang B, An J, Wang J, Tian J . Genome sequence of the milbemycin-producing bacterium Streptomyces bingchenggensis. J Bacteriol. 2010; 192(17):4526-7. PMC: 2937363. DOI: 10.1128/JB.00596-10. View

17.

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

18.

Pfeifer B, Hu Z, Licari P, Khosla C . Process and metabolic strategies for improved production of Escherichia coli-derived 6-deoxyerythronolide B. Appl Environ Microbiol. 2002; 68(7):3287-92. PMC: 126764. DOI: 10.1128/AEM.68.7.3287-3292.2002. View

19.

Seo M, Zhu D, Endo S, Ikeda H, Cane D . Genome mining in Streptomyces. Elucidation of the role of Baeyer-Villiger monooxygenases and non-heme iron-dependent dehydrogenase/oxygenases in the final steps of the biosynthesis of pentalenolactone and neopentalenolactone. Biochemistry. 2011; 50(10):1739-54. PMC: 3051010. DOI: 10.1021/bi1019786. View

20.

Cane D, He X, Kobayashi S, Omura S, Ikeda H . Geosmin biosynthesis in Streptomyces avermitilis. Molecular cloning, expression, and mechanistic study of the germacradienol/geosmin synthase. J Antibiot (Tokyo). 2006; 59(8):471-9. DOI: 10.1038/ja.2006.66. View