Sebekia benihana에서 Streptomyces coelicolor SCO4967 유전자 도입을 통한 하이드록실 사이클로스포린 A의 생전환
Improvement of Cyclosporin A Hydroxylation in Sebekia benihana by Conjugational Transfer of Streptomyces coelicolor SCO4967, a Secondary Metabolite Regulatory Gene.
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Actinomycetes are Gram-positive soil bacteria and one of the most important industrial microorganisms due to superior biosynthetic capabilities of many valuable secondary metabolites as well as production of various valuable bioconversion enzymes. Among them are cytochrome P450 hydroxylase (CYP), which are hemoproteins encoded by a super family of genes, are universally distributed in most of the organisms from all biological kingdoms. Actinomycetes are a rich source of soluble CYP enzymes, which play critical roles in the bioactivation and detoxification of a wide variety of metabolite biosynthesis and xenobiotic transformation. Cyclosporin A (CyA), one of the most commonly-prescribed immunosuppressive drugs, was previously reported to be hydroxylated at the position of 4th N-methyl leucine by a rare actinomycetes called Sebekia benihana, leading to display different biological activity spectrum such as loss of immunosuppressive activities yet retaining hair growth-stimulating side effect. In order to improve this regio-selective CyA hydroxylation in S. benihana, previously-identified several secondary metabolite up-regulatory genes from Streptomyces coelicolor and S. avermitilis were heterologously overexpressed in S. benihana using an ermE *promoter-containing Streptomyces integrative expression vector. Among tested, SCO4967 encoding a conserved hypothetical protein significantly stimulated region-specific CyA hydroxylation in S. benihana, implying that some common regulatory systems functioning in both biosynthesis and bioconversion of secondary metabolite might be present in different actinomycetes species.
Abstract
Actinomycetes are Gram-positive soil bacteria and one of the most important industrial microorganisms due to superior biosynthetic capabilities of many valuable secondary metabolites as well as production of various valuable bioconversion enzymes. Among them are cytochrome P450 hydroxylase (CYP), which are hemoproteins encoded by a super family of genes, are universally distributed in most of the organisms from all biological kingdoms. Actinomycetes are a rich source of soluble CYP enzymes, which play critical roles in the bioactivation and detoxification of a wide variety of metabolite biosynthesis and xenobiotic transformation. Cyclosporin A (CyA), one of the most commonly-prescribed immunosuppressive drugs, was previously reported to be hydroxylated at the position of 4th N-methyl leucine by a rare actinomycetes called Sebekia benihana, leading to display different biological activity spectrum such as loss of immunosuppressive activities yet retaining hair growth-stimulating side effect. In order to improve this regio-selective CyA hydroxylation in S. benihana, previously-identified several secondary metabolite up-regulatory genes from Streptomyces coelicolor and S. avermitilis were heterologously overexpressed in S. benihana using an ermE *promoter-containing Streptomyces integrative expression vector. Among tested, SCO4967 encoding a conserved hypothetical protein significantly stimulated region-specific CyA hydroxylation in S. benihana, implying that some common regulatory systems functioning in both biosynthesis and bioconversion of secondary metabolite might be present in different actinomycetes species.
참고문헌 (32)
- Asai, K, "DNA microarray analysis of Bacillus subtilis sigma factors of extracytoplasmic function family", FEMS Microbiol. Lett., 220, pp.155~160 (2003)
- Bìhal,V, "Bioactive products from Streptomyces", Adv. Appl. Microbiol, 47, pp.113~156 (2000)
- Cao, M, "Regulation of the Bacillus subtilis extracytoplasmic function protein óY and its target promoters", J. Bacteriol., 185, pp.4883~4890 (2003)
- Choi, S.-U, "Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Kitasatospora setae, a bafilomycin B1 producer", Arch. Microbiol., 181, pp.294~298 (2004)
- Delort, A. M, "Microbial conversion of nigericin in three successive steps, by Sebekia benihana", J. Antibiot., 41, pp.916~924 (1988)
- Dörner, E, "Properties of 2-oxoglutarate: Ferredoxin oxidoreductase from Thauera aromatica and its role in enzymatic reduction of the aromatic ring", J. Bacteriol., 184, pp.3975~3983 (2002)
- Duong Cac Thi Phung, "Functional Expression of SAV3818, a Putative TetR-Family Transcriptional Regulatory Gene from Streptomyces avermitilis, Stimulates Antibiotic Production in Streptomyces Species", Journal of Microbiology and Biotechnology, 19(2), pp.136~139 (2009), 한국미생물·생명공학회
- GuagueÌre, E, "Cyclosporin A: A new drug in the field of canine dermatology", Vet. Dermatol., 15, pp.61~74 (2004)
- Guilfoile, P. G, "A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin", Proc. Natl. Acad. Sci. U. S. A., 88, pp.8553~8557 (1991)
- Hasegawa, H, "TetR-type transcriptional regulator VtpR functions as a global regulator in Vibrio tubiashii", Appl. Environ. Microbiol, 75, pp.7602~7609 (2009)
- Helmann,J.D, "The extracytoplasmic function (ECF) sigma factors", Adv. Microb. Physiol, 46, pp.47~110 (2002)
- Hopwood, D. A, "Genetic manipulation of streptomyces", A laboratory manual, 161~211 (1985)
- Hughes, N. J, "Helicobacter pylori porCDAB and oorDABC genes encode distinct pyruvate flavodoxin and 2-oxoglutarate: Acceptor oxidoreductases which mediate electron transport to NADP", J. Bacteriol, 180, pp.1119~1128 (1998)
- IM, JONG-HYUK, "Comparative Transcriptome Analysis for Avermectin Overproduction viaStreptomyces avermitilis Microarray System", Journal of Microbiology and Biotechnology, 17(3), pp.534~538 (2007), 한국미생물·생명공학회
- Kang, S.-H, "Interspecies DNA microarray analysis identifies WblA as a pleiotropic down-regulator of antibiotic biosynthesis in Streptomyces", J. Bacteriol., 189, pp.4315~4319 (2007)
- Kieser, T, "Streptomyces genetics: A laboratory manual", John Innes Foundation, ~ (2000)
- Kuhnt, M, "Microbial biotransformation products of cyclosporin A", J. Antibiot, 49, pp.781~787 (1996)
- Lum, A. M, "Reverse engineering of industrial pharmaceuticalproducing actinomycete strains using DNA microarrays", Metab. Eng., 6, pp.186~196 (2004)
- Noh, J.-H, "Isolation and genetic manipulation of the antibiotic down-regulatory gene, wblA ortholog for doxorubicin-producing Streptomyces strain improvement", Appl. Microbiol. Biotechnol., 86, pp.1145~1153 (2010)
- Paradkar, A, "Streptomyces genetics: A genomic perspective", Crit. Rev. Biotechnol., 23, pp.1~27 (2003)
- Jung-Hye Roe, "Identification of Genes for Mycothiol Biosynthesisin Streptomyces coelicolor A3(2)", The Journal of Microbiology, 44(1), pp.121~125 (2006), 한국미생물학회
- PARK, NAM SIL, "Characterization and Culture Optimization of Regiospecific CyclosporinHydroxylation in Rare Actinomycetes Species", Journal of Microbiology and Biotechnology, 15(1), pp.188~191 (2005), 한국미생물·생명공학회
- PARK, NAM-SIL, "Heterologous Expression of Novel Cytochrome P450 Hydroxylase Genes from Sebekia benihana", Journal of Microbiology and Biotechnology, 16(2), pp.295~298 (2006), 한국미생물·생명공학회
- Ramos, J. L, "The TetR family of transcriptional repressors", Microbiol. Mol. Biol. Rev., 69, pp.326~356 (2005)
- Rawat, M, "Inactivation of mshB, a key gene in the mycothiol biosynthesis pathway in Mycobacterium smegmatis", Microbiology, 149, pp.1341~1349 (2003)
- Rawat, M, "Targeted mutagenesis of the Mycobacterium smegmatis mca gene, encoding a mycothiol-dependent detoxification protein", J. Bacteriol., 186, pp.6050~6058 (2004)
- Resch, K, "Molecular mechanisms of the immunosuppressive action of cyclosporin A", Int. J. Immunopharmacol., 19, pp.579~585 (1997)
- Roberts, G. A, "Identification of a new class of cytochrome P450 from a Rhodococcus sp", J. Bacteriol., 184, pp.3898~3908 (2002)
- Sambrook J, "Molecular cloning. A laboratory manual" (1989), Cold Spring Harbor Laboratory Press
- Schmitt, L, "Structure and mechanism of ABC transporters", Curr. Opin. Struct. Biol., 12, pp.754~760 (2002)
- Van Veen, H. W, "The homodimeric ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating two-site (two-cylinder engine) mechanism", EMBO J., 19, pp.2503~2514 (2000)
- Vaufrey, F, "G. Dauphin. 1990. Bioconversion of monensin by a soil bacterium, Sebekia benihana", J. Antibiot, 43, pp.1189~1191 (1990)