Myxococcus stipitatus DSM 14675의 melithiazol 생합성 유전자 분석
Analysis of the Melithiazol Biosynthetic Gene Cluster in Myxococcus stipitatus DSM 14675
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초록
Melithiazols are antifungal substances produced by the myxobacteria Melitangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. Melithiazol biosynthetic genes have been identified in M. lichenicola, but not in A. gephyra and M. stipitatus until now. We identified a 37.3-kb melithiazol biosynthetic gene cluster from M. stipitatus DSM 14675 using genome sequence analysis and mutational analysis. The cluster is comprised of 9 genes (MYSTI_04973 to MYSTI_04965) that encode 4 polyketide synthase modules, 3 nonribosomal peptide synthase modules, a putative fumarylacetoacetate hydrolase, a putative S-adenosylmethionine- dependent methyltransferase, and a putative nitrilase. Disruption of the MYSTI_04972 or MYSTI_ 04973 gene by plasmid insertion resulted in defective melithiazol production. The organization of the melithiazol biosynthetic modules encoded by 8 genes from MYSTI_04972 to MYSTI_04965 was similar to that in M. lichenicola Me l46. However, the loading module encoded by the first gene (MYSTI_04973) was different from that of M. lichenicola Me l46, explaining the difference in the production of melithiazol derivatives between the M. lichenicola Me l46 and M. stipitatus strains.
Abstract
Melithiazols are antifungal substances produced by the myxobacteria Melitangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. Melithiazol biosynthetic genes have been identified in M. lichenicola, but not in A. gephyra and M. stipitatus until now. We identified a 37.3-kb melithiazol biosynthetic gene cluster from M. stipitatus DSM 14675 using genome sequence analysis and mutational analysis. The cluster is comprised of 9 genes (MYSTI_04973 to MYSTI_04965) that encode 4 polyketide synthase modules, 3 nonribosomal peptide synthase modules, a putative fumarylacetoacetate hydrolase, a putative S-adenosylmethionine- dependent methyltransferase, and a putative nitrilase. Disruption of the MYSTI_04972 or MYSTI_ 04973 gene by plasmid insertion resulted in defective melithiazol production. The organization of the melithiazol biosynthetic modules encoded by 8 genes from MYSTI_04972 to MYSTI_04965 was similar to that in M. lichenicola Me l46. However, the loading module encoded by the first gene (MYSTI_04973) was different from that of M. lichenicola Me l46, explaining the difference in the production of melithiazol derivatives between the M. lichenicola Me l46 and M. stipitatus strains.
참고문헌 (23)
- 안동주, "점액세균 Myxococcus stipitatus KYC4013에 의한 생리활성물질생산", 한국미생물·생명공학회지, 42(4), pp.331~338 (2014), 한국미생물·생명공학회[DOI]
- Blin K, "antiSMASH 2.0 — a versatile platform for genome mining of secondary metabolite producers", Nucl. Acids Res, 41, pp.W204~W212 (2013)
- Böhlendorf B, "Antibiotics from gliding bacteria, 85 Melithiazols A–N: new antifungal α-methoxyacrylates from myxobacteria", Eur. J. Org. Chem, 1999, pp.2601~2608 (1999)
- Feng Z, "Construction of a bacterial artificial chromosome library for a myxobacterium of the genus Cystobacter and characterization of an antibiotic biosynthetic gene cluster", Biosci. Biotechnol. Biochem, 69, pp.1372~1380 (2005)
- Hagen DC, "Synergism between morphogenetic mutants of Myxococcus xanthus", Dev. Biol, 64, pp.284~296 (1978)
- Huntley S, "Complete genome sequence of Myxococcus stipitatus strain DSM 14675, a fruiting myxobacterium", Genome Announc, 1, pp.e0010013~ (2013)
- Larkin MA, "Clustal W and Clustal X version 2.0", Bioinformatics, 23, pp.2947~2948 (2007)
- Marchler-Bauer A, "CDD: NCBI's conserved domain database", Nucl. Acids Res, 43, pp.D222~D226 (2015)
- Medema MH, "antiSMASH: Rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters", Nucleic Acids Res, 39, pp.W339~W346 (2011)
- Minowa Y, "Comprehensive analysis of distinctive polyketide and nonribosomal peptide structural motifs encoded in microbial genomes", J. Mol. Biol, 368, pp.1500~1517 (2007)
- Müller I, "Biochemical characterization of MelJ and MelK", FEBS J, 273, pp.3768~3778 (2006)
- Ojika M, "Cystothiazoles A and B, new bithiazole-type antibiotics from the myxobacterium Cystobacter fuscus", J. Antibiot, 51, pp.275~281 (1998)
- Reichenbach H, "Bergey's Manual of Systematic Bacteriology", pp.1059~1144 (2005), Bergey's Manual Trust
- Sasse F, "Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties", J. Antibiot, 52, pp.721~729 (1999)
- 신혜진, "Corallococcus와 Myxococcus 속 점액세균 균주들에 의한 항균 물질의 생산", 한국미생물·생명공학회지, 41(1), pp.44~51 (2013), 한국미생물·생명공학회[DOI]
- Silakowski B, "New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4", 3-1, 1999, pp.274, 37391~37399
- Suzukia Y, "Cystothiazoles C-F, new bithiazole-type antibiotics from the myxobacterium Cystobacter fuscus", Tetrahedron, 54, pp.11399~11404 (1998)
- Tamura K, "MEGA6: Molecular evolutionary genetics analysis version 6.0", Mol. Biol. Evol, 30, pp.2725~2729 (2013)
- Trowitzsch W, "Myxothiazol, an antibiotic from Myxococcus fulvus (myxobacterales). II. structure elucidation", J. Antibiot, 33, pp.1480~1490 (1980)
- Weinig S, "Melithiazol biosynthesis:further insights into myxobacterial PKS", NRPS systems and evidence for a new subclass of methyl transferases, 2003, pp.10, 939~952
- Weissman KJ, "Myxobacterial secondary metabolites:bioactivities and modes-of-action", Nat. Prod. Rep, 27, pp.1276~1295 (2010)
- Williams GJ, "Engineering polyketide synthases and nonribosomal peptide synthetases", Curr. Opin. Struct. Biol, 23, pp.603~612 (2013)
- Yadav G, "Computational approach for prediction of domain organization and substrate specificity of modular polyketide synthases", J. Mol. Biol, 328, pp.335~363 (2003)
