• Microbiology and Biotechnology Letters
• /
• v.49 no.4
• /
• pp.493-500
• /
• 2021

Argyrins are a group of anticancer and antibacterial octapeptide bioactive substances isolated from myxobacteria. In this study, we showed that the myxobacterium Archangium gephyra MEHO_001, isolated in Korea, produces argyrins A and B. MEHO_001 cells tend to aggregate when cultured in liquid media. Hence, a dispersion mutant, MEHO_002, was isolated from MEHO_001. The MEHO_002 strain produced approximately 3.5 times more argyrins than that produced by the wild-type strain MEHO_001. We determined the whole-genome sequence of A. gephyra MEHO_002 and identified a putative argyrin biosynthetic gene cluster comprising five genes, arg1-arg5, encoding non-ribosomal peptide synthases and tailoring enzymes. Inactivation of arg2 by plasmid insertion disrupted argyrin production. The amino acid sequences of the proteins encoded by arg2-arg5 of A. gephyra MEHO_002 were 90-98% similar to those encoded by the argyrin biosynthetic genes of Cystobacter sp. SBCb004, an argyrin-producing myxobacterium with identical domain organization.

• Microbiology and Biotechnology Letters
• /
• v.49 no.3
• /
• pp.458-465
• /
• 2021

Tubulysins are a group of bioactive secondary metabolites from myxobacteria exhibiting strong anticancer activity against various cancer cell lines. In this study, we describe the identification of putative tubulysin biosynthetic gene clusters (tubA~tubF) in the genome sequences of two tubulysin-producing myxobacterial strains, Archangium gephyra MEHO_002 and MEHO_004. The inactivation of the putative tubulysin biosynthetic genes resulted in a tubulysin-production defect. The DNA sequences of the A. gephyra MEHO_002 and MEHO_004 tubulysin biosynthetic genes were 97% identical, and the amino acid sequences of the encoded proteins shared a similarity of 97-100%. The nucleotide sequences of the tubulysin biosynthetic gene clusters in MEHO_002 and MEHO_004 were 86% identical to that in Cystobacter sp. SBCb004 known as a tubulysin-producing myxobacterium, and the organization of the clusters was identical except for the lack of a tubZ gene in the clusters in MEHO_002 and MEHO_004. The amino acid sequences of the proteins encoded by each gene were 88-97% similar to those encoded by SBCb004, and the domain compositions of the proteins were also identical.

• Microbiology and Biotechnology Letters
• /
• v.49 no.1
• /
• pp.32-38
• /
• 2021

Tubulysins are a group of secondary metabolites produced by myxobacteria that inhibit the function of the eukayotic cytoskeleton. We developed a pair of PCR primers that specifically amplified tubulysin biosynthetic genes. Using these primers, eight out of the eighty-one strains of myxobacteria belonging to the Cystobacteraceae family that harbored putative tubulysin biosynthetic genes were screened through PCR analysis. The selected strains included two Archangium gephyra, two Stigmatella sp., two Vitiosangium cumulatum, and two unidentified myxobacteria. LC-MS analysis of the culture extracts from the selected strains revealed that A. gephyra KYC4066 produced putative tubulysin A and B.

• Microbiology and Biotechnology Letters
• /
• v.44 no.3
• /
• pp.391-399
• /
• 2016

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 non-ribosomal 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.