• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1101-1108
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• 2008

Geldanamycin and its analogs are important anticancer agents that inhibit the newly targeted heat-shock protein (Hsp) 90, which is a chaperone protein in eukaryotic cells. To resolve which geldanamycin biosynthetic genes are responsible for particular post-polyketide synthase (PKS) processing steps and in which order the reactions occur, we individually inactivated candidate genes in Streptomyces hygroscopicus subsp. duamyceticus JCM4427 and isolated and elucidated the structures of intermediates from each mutant. The results indicated that gel7 governs at least one of the benzoquinone ring oxidation steps. The gel16 was found to be involved in double-bond formation between C-4 and C-5 of 4,5-dihydrogeldanamycin, which confirmed our previous findings that this double bond is reduced during the post-PKS modification of the polyketide assembly. In addition, pro-geldanamycin, which does not possess a double bond at C-4/5, was purified from the gel7 and gel8 double-gene-inactivated mutant.

• Journal of Applied Biological Chemistry
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• v.59 no.1
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• pp.45-47
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• 2016

Two Monascus purpureus genomes lack the monacolin K biosynthesis locus (mok), while Monascus species are generally assumed to be monacolin K producers. These M. purpureus harbor a fusion of mokA and mokB orthologues. This finding suggests that an ancestral mok locus underwent a deletion event in the M. purpureus genome.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.684-685
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• 2005

• Research in Plant Disease
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• v.20 no.3
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• pp.216-218
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• 2014

Lysobacter antibiocus HS124 is a chitinase-producing rhizobacterium with proven capacities to suppress plant diseases. Bacterial cultures of L. antibioticus HS124 showed strong biocontrol efficacies against various plant diseases compared to those of bacterial cultures of Bacillus subtilis QST713 which is an active ingredient of a commercial biopesticide, Serenade. Here, we report the draft genome sequence and automated annotation of strain HS124. This draft genome sequence indicates the novelty of L. antibiocus HS124 and a subset of gene functions that may be related to its biocontrol activities.

• 한국균학회소식:학술대회논문집
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• 2016.05a
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• pp.27-27
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• 2016

The ascomycete fungus Fusarium graminearum is the most common pathogen of Fusarium head blight (FHB), a devastating disease for major cereal crops worldwide. FHB causes significant crop losses by reducing grain yield and quality as well as contaminating cereals with trichothecenes and zearalenone (ZEA) that pose a serious threat to animal health and food safety. ZEA is a causative agent of hyperestrogenic syndrome in mammals and can result in reproductive disorders in farm animals. In F. graminearum, the ZEA biosynthetic cluster is composed of four genes, PKS4, PKS13, ZEB1, and ZEB2, which encode a reducing polyketide synthase, a nonreducing polyketide synthase, an isoamyl alcohol oxidase, and a transcription factor, respectively. Although it is known that ZEB2 primarily acts as a regulator of ZEA biosynthetic cluster genes, the mechanism underlying this regulation remains undetermined. In this study, two isoforms (ZEB2L and ZEB2S) from the ZEB2 gene in F. graminearum were characterized. It was revealed that ZEB2L contains a basic leucine zipper (bZIP) DNA-binding domain at the N-terminus, whereas ZEB2S is an N-terminally truncated form of ZEB2L that lacks the bZIP domain. Interestingly, ZEA triggered the induction of both ZEB2L and ZEB2S transcription. In ZEA producing condition, the expression of ZEB2S transcripts via alternative promoter usage was directly or indirectly initiated by ZEA. Physical interaction between ZEB2L and ZEB2L as well as between ZEB2L and ZEB2S was observed in the nucleus. The ZEB2S-ZEB2S interaction was detected in both the cytosol and the nucleus. ZEB2L-ZEB2L oligomers activated ZEA biosynthetic cluster genes, including ZEB2L. ZEB2S inhibited ZEB2L transcription by forming ZEB2L-ZEB2S heterodimers, which reduced the DNA-binding activity of ZEB2L. This study provides insight into the autoregulation of ZEB2 expression by alternative promoter usage and a feedback loop during ZEA production.

• Journal of Microbiology and Biotechnology
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• v.29 no.10
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• pp.1570-1579
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• 2019

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in $g{\alpha}1{\Delta}$, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.

• Journal of Microbiology and Biotechnology
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• v.29 no.7
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• pp.1144-1154
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• 2019

There have been several studies regarding lichen-associated bacteria obtained from diverse environments. Our screening process identified 49 bacterial species in two lichens from the Himalayas: 17 species of Actinobacteria, 19 species of Firmicutes, and 13 species of Proteobacteria. We discovered five types of strong antimicrobial agent-producing bacteria. Although some strains exhibited weak antimicrobial activity, NP088, NP131, NP132, NP134, and NP160 exhibited strong antimicrobial activity against all multidrug-resistant strains. Polyketide synthase (PKS) fingerprinting revealed results for 69 of 148 strains; these had similar genes, such as fatty acid-related PKS, adenylation domain genes, PfaA, and PksD. Although the association between antimicrobial activity and the PKS fingerprinting results is poorly resolved, NP160 had six types of PKS fingerprinting genes, as well as strong antimicrobial activity. Therefore, we sequenced the draft genome of strain NP160, and predicted its secondary metabolism using antiSMASH version 4.2. NP160 had 46 clusters and was predicted to produce similar secondary metabolites with similarities of 5-100%. Although NP160 had 100% similarity with the alkylresorcinol biosynthetic gene cluster, our results showed low similarity with existing members of this biosynthetic gene cluster, and most have not yet been revealed. In conclusion, we expect that lichen-associated bacteria from the Himalayas can produce new secondary metabolites, and we found several secondary metabolite-related biosynthetic gene clusters to support this hypothesis.

• Journal of Microbiology and Biotechnology
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• v.26 no.9
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• pp.1636-1642
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• 2016

Phenalamide is a bioactive secondary metabolite produced by Myxococcus stipitatus. We identified a 56 kb phenalamide biosynthetic gene cluster from M. stipitatus DSM 14675 by genomic sequence analysis and mutational analysis. The cluster is comprised of 12 genes (MYSTI_04318- MYSTI_04329) encoding three pyruvate dehydrogenase subunits, eight polyketide synthase modules, a non-ribosomal peptide synthase module, a hypothetical protein, and a putative flavin adenine dinucleotide-binding protein. Disruption of the MYSTI_04324 or MYSTI_04325 genes by plasmid insertion resulted in a defect in phenalamide production. The organization of the phenalamide biosynthetic modules encoded by the fifth to tenth genes (MYSTI_04320-MYSTI_04325) was very similar to that of the myxalamid biosynthetic gene cluster from Stigmatella aurantiaca Sg a15, as expected from similar backbone structures of the two substances. However, the loading module and the first extension module of the phenalamide synthase encoded by the first to fourth genes (MYSTI_04326-MYSTI_04329) were found only in the phenalamide biosynthetic gene cluster from M. stipitatus DSM 14675.

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

• Mycobiology
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• v.51 no.1
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• pp.36-48
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• 2023

Xanthoria elegans is a lichen symbiosis, that inhabits extreme environments and can absorb UV-B. We reported the de novo sequencing and assembly of X. elegans genome. The whole genome was approximately 44.63 Mb, with a GC content of 40.69%. Genome assembly generated 207 scaffolds with an N50 length of 563,100 bp, N90 length of 122,672 bp. The genome comprised 9,581 genes, some encoded enzymes involved in the secondary metabolism such as terpene, polyketides. To further understand the UV-B absorbing and adaptability to extreme environments mechanisms of X. elegans, we searched the secondary metabolites genes and gene-cluster from the genome using genome-mining and bioinformatics analysis. The results revealed that 7 NR-PKSs, 12 HR-PKSs and 2 hybrid PKS-PKSs from X. elegans were isolated, they belong to Type I PKS (T1PKS) according to the domain architecture; phylogenetic analysis and BGCs comparison linked the putative products to two NR-PKSs and three HR-PKSs, the putative products of two NR-PKSs were emodin xanthrone (most likely parietin) and mycophelonic acid, the putative products of three HR-PKSs were soppilines, (+)-asperlin and macrolactone brefeldin A, respectively. 5 PKSs from X. elegans build a correlation between the SMs carbon skeleton and PKS genes based on the domain architecture, phylogenetic and BGC comparison. Although the function of 16 PKSs remains unclear, the findings emphasize that the genes from X. elegans represent an unexploited source of novel polyketide and utilization of lichen gene resources.