• KSBB Journal
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• v.20 no.5 s.94
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• pp.376-382
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• 2005

Avermectin (AVM) $B_{1a}$ produced by Streptomyces avermitilis via polyketide pathway is a secondary metabolite with powerful anthelmintic and insecticidal activities, thus being used as an efficient agent in the field of agriculture and animal health. It has been reported that a precursor for AVM $B_{1a}$ biosynthesis was isoleucine and the biosynthetic pathway of AVM $B_{1a}$ was closely similar to that of fatty acid. Based on understanding of the biosynthetic pathway of AVM $B_{1a}$, we intended to screen various mutants resistant against O-methyl threonine (OMT), an isoleucine-anti metabolite, and/or mutants resistant against p-fluoro phenoxy acetic acid (pFAC), an inhibitor of fatty acid biosynthesis. It was inferred that these mutants could produce AVM $B_{1a}$ more efficiently, due to the acquired capability of not only overproducing isoleucine intracellularly but also channelling metabolized carbon-sources into the polyketide pathway, thus leading to enhanced biosynthesis of AVM $B_{1a}$. The resulting mutant (PFA-1 strain) resistant against 100 ppm of pFAC was able to produce approximately 42 fold higher amount of AVM $B_{1a}$ compared to the parallel mother strain (4,200 vs. 100 units/l). In addition, through the process of continuous strain improvement program carried out by gradually increasing the OMT concentration, it was possible to obtain a more attractive mutant with greater AVM $B_{1a}$ production capacity (9,000 units/l). Notable was that significantly higher producer (12,000 units/l) could be selected through further screening of the resistant mutants, this time, to even higher concentration of PFAC. Meanwhile, through the analysis of AVM Bla production histograms (i.e., number of strains according to their AVM $B_{1a}$ biosynthetic ability) for the earlier strains in comparison with the high producers having the characteristics of resistance to OMT and pFAC, it was found that production stability of the high-yielding producers were remarkably improved, as demonstrated by the fact that larger proportion of the mutated strains had greater capability of AVM $B_{1a}$ biosynthesis ($71\%$ in the range between 5,000 and 7,000 units/L; $47\%$ in the range between 6,000 and 7,000 units/l). Based on these consequences, it was concluded that the rational screening strategy based on the understanding of the biosynthetic pathway of AVM $B_{1a}$ was very effective in obtaining high-yielding mutants with the features of enhanced production stability.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.596-596
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• 2003

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.119-119
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• 2005

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.453-455
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• 2003

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.662-662
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• 2005

• Applied Biological Chemistry
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• v.32 no.1
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• pp.57-63
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• 1989

Cigarette beetle(Lacioderma serricornine F.) is a serious pest of cured tobacco leaves. Of its pheromonal components, serricornin shows the strongest sexual stimulation. Other substances contribute as the supplementary factors cooperating with this component in the copulation of cigarette beetle. From spectroscopic evidence and synthetic studies, the structure of natural serricornin has been determined to be (4S,4S,7S)-4, 6-dimethyl-7-hydroxynonan-3-one. It has been suggested that the pheromonal components isolated from this beetle may be derived from polyketide biosynthesis. Two nonasymmetric syntheses of serricornin will be reviewed in detail.

• Molecules and Cells
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• v.22 no.2
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• pp.154-162
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• 2006

The entire gene cluster involved in the biosynthesis of angucyclines Sch 47554 and Sch 47555 was cloned, sequenced, and characterized. Analysis of the nucleotide sequence of genomic DNA spanning 77.5-kb revealed a total of 55 open reading frames, and the deduced products exhibited strong sequence similarities to type II polyketide synthases, deoxysugar biosynthetic enzymes, and a variety of accessory enzymes. The involvement of this gene cluster in the pathway of Sch 47554 and Sch 47555 was confirmed by genetic inactivation of the aromatase, including a portion of the ketoreductase, which was disrupted by inserting the thiostrepton gene.

• KSBB Journal
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• v.24 no.2
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• pp.163-169
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• 2009

Lovastatin (also known as Mevinolin, Mevacor, and Monacolin K), an inhibitor of the HMG-CoA reductase produced by Aspergillus terreus and other fungi, is used to reduce serum cholesterol levels in human beings. It is derived biosynthetically from two polyketides. One of these is a nonaketide that undergoes cyclization at a hexahydronaphthalene ring system, and the other is a simple diketide, 2-methylbutyrate. Two primer pairs were designed based on the amino acid sequences of lovastatin polyketide synthase and lovastatin diketide synthase for the PCR screening of lovastatin-producing strains. Among the seven selected strains, SJ-2 evidenced the highest level of lovastatin production in both liquid and solid cultures. Soybeans with SJ-2 were treated via 1 hour of heat shock at $30^{\circ}C$ for the mass production of lovastatin. The heat-treated soybeans were inoculated on rice bran and the koji extract was obtained after 15 days of incubation. It yielded the highest level of lovastatin production among the strains, and also evidenced 75% inhibition activity against HMG-CoA reductase. We developed an efficient PCR screening method for lovastatin-producing strains, using lovastatin biosynthesis genes.

• 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.

• Genomics & Informatics
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• v.6 no.4
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• pp.223-226
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• 2008

We introduce a computational approach for analysis of glycosylation in Post-PKS tailoring steps. It is a computational method to predict the deoxysugar biosynthesis unit pathway and the substrate specificity of glycosyltransferases involved in the glycosylation of polyketides. In this work, a directed and weighted graph is introduced to represent and predict the deoxysugar biosynthesis unit pathway. In addition, a homology based gene clustering method is used to predict the substrate specificity of glycosyltransferases. It is useful for the rational design of polyketide natural products, which leads to in silico drug discovery.