Abstract
Two regulator genes, metK1-sp and afsR-sp, from Streptomyces peucetius ATCC 27952 were heterologously expressed in S. venezuelae ATCC 15439, to produce 14-membered pikromycin antibiotics. The production of pikromycin was increased by 1.6-fold and 2.6-fold by the expression of metK1-sp and afsR-sp, respectively. The overexpression of metK1-sp and afsR-sp in S. venezuelae stimulated the expression of the pathway-specific regulatory genes, pikD and ketosynthase, as demonstrated by RT-PCR. The elevated transcripts of the pikD and ketosynthase genes were consistent with the enhanced production of pikromycin.
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References
Agouridas C, Denis A, Auger JM et al (1998) Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives) a new class of antibacterials highly potent against macrolide-resistant and susceptible respiratory pathogens. J Med Chem 41:4080–4100
Basundhara S, Oh TJ, Lamichhane R et al (2004) Neocarzinostatin naphthoate synthase: an unique iterative type I PKS from neocarzinostatin producer Streptomyces carzinostaticus. FEBS Lett 566:201–206
Bisang C, Long PF, Cortés J et al (1999) A chain initiation factor common to both modular and aromatic polyketide synthases. Nature 401:502–505
Chen H, Yamase H, Murakami K et al (2002) Expression, purification, and characterization of two N,N-dimethyltransferases, TylM1 and DesVI, involved in the biosynthesis of mycaminose and desosamine. Biochemistry 41:9165–9183
Horinouchi S (2003) AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2). J Ind Microbiol Biotechnol 30:462–467
Kieser T, Bibb MJ, Buttner MJ et al (2000) Practical Streptomyces genetics. The John Innes Foundation, Norwich
Kim DJ, Huh JH, Yang YY et al (2003) Accumulation of S-adenosyl-l-methionine enhances production of actinorhodin but inhibits sporulation in Streptomyces lividans TK23. J Bacteriol 185:592–600
Lee SK, Hong JSJ, Choi CY et al (2006) Enhanced production of hydroxylated macrolides from pikromycin pathway of Streptomyces venezuelae. Enzyme Microb Technol 39:778–782
Lee PC, Umeyama T, Horinouchi S (2002) afsS is a target of AfsR, a transcriptional factor with ATPase activity that globally controls secondary metabolism in Streptomyces coelicolor A3(2). Mol Microbiol 43:1413–1430
Okamoto S, Lezhava A, Hosaka T et al (2003) Enhanced expression of S-adenosylmethionine synthetase causes overproduction of actinorhodin in Streptomyces coelicolor A3 (2). J Bacteriol 185:601–609
Parajuli N, Hung TV, Ishida K et al (2005) Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952. Res Microbiol 156:707–712
Shin SK, Park HS, Kwon HJ et al (2007) Genetic characterization of two S-adenosylmethionine-induced ABC transporters reveals their roles in modulations of secondary metabolism and sporulation in Streptomyces coelicolor M145. J Microbiol Biotechnol 17:1818–1825
Tanaka A, Takano Y, Ohnishi Y et al (2007) AfsR recruits RNA polymerase to the afsS promoter: a model for transcriptional activation by SARPs. J Mol Biol 369:322–333
Umeyama T, Lee PC, Horinouchi S (2002) Protein serine/threonine kinases in signal transduction for secondary metabolism and morphogenesis in Streptomyces. Appl Microbiol Biotechnol 59:419–425
Wang Y, Boghigian BA, Pfeifer BA (2007) Improving heterologous polyketide production in Escherichia coli by overexpression of an S-adenosylmethionine synthetase gene. Appl Microbiol Biotechnol 77:367–373
Wilson DJ, Xue Y, Reynolds KA et al (2001) Characterization and analysis of the PikD regulatory factor in the pikromycin biosynthetic pathway of Streptomyces venezuelae. J Bacteriol 183:3468–3475
Xue Y, Zhao L, Liu HW et al (1998) A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: Architecture of metabolic diversity. Biochemistry 95:12111–12116
Zhao XQ, Jin YY, Kwon HJ et al (2006) S-Adenosylmethionine (SAM) regulates antibiotic biosynthesis in Streptomyces spp. in a mode independent of its role as a methyl donor. J Microbiol Biotechnol 16:927–932
Acknowledgments
The work was supported by a medium-term strategic technology development grant from the Republic of Korea to JKS and the authors thank to the Korea Research Foundation (KRF) for the graduate (Ph D) student scholarship.
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Maharjan, S., Oh, TJ., Lee, H.C. et al. Heterologous expression of metK1-sp and afsR-sp in Streptomyces venezuelae for the production of pikromycin. Biotechnol Lett 30, 1621–1626 (2008). https://doi.org/10.1007/s10529-008-9735-0
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DOI: https://doi.org/10.1007/s10529-008-9735-0