The advances of genomic sequence
analyses and genome mining tools
have enabled the exploration of untapped microbial natural products.
Through genome mining studies to discover cryptic natural products,
we found biosynthetic genes encoding a new lasso peptide in the genome
sequence of a soil bacterium, Streptomyces sp. KCB13F003
isolated from Ulleung Island (a small volcanic island), Korea. The
production and purification of the encoded peptide, named ulleungdin,
were achieved by optimizing the culture conditions followed by LC-MS-targeted
isolation. Structure elucidation was performed by NMR spectroscopic
and MS spectrometric analyses and chemical means (Marfey’s
and GITC derivatizations), proving ulleungdin to be a new 15-mer class
II lasso peptide with a threaded structure. Biological evaluation
with the cell invasion assay and time-lapse cell tracking analysis
revealed that ulleungdin has significant inhibitory activities against
cancer cell invasion and migration.
A new series of geldanamycin derivatives were synthesized using a semi-synthetic approach involving genetically engineered biosynthetic intermediates. These analogues were then evaluated for anti-proliferation activity in human cancer cell lines, SK-Br3 and SK-Ov3. Most of the synthesized compounds exhibited potent in vitro anti-proliferation activity toward both cell lines. Such compounds potently inhibited the expression of the Hsp90 client protein ErbB2.
The gene encoding aklavinone 11-hydroxylase of Streptomyces peucetius subsp. caesius ATCC 27952 was cloned and sequenced. The deduced amino acid sequence of the gene contains at least two common motifs of well-conserved amino acid sequences of several flavin-type bacterial hydroxylases. The hydroxylase gene is apparently transcribed from a single transcriptional start point. The phenotype of a dnrF mutant generated by gene disruption supports the idea that the dnrF gene encodes aklavinone 11-hydroxylase.
A taxonomic study was performed on two isolates, designated strains MK-B5T and MK-B7, isolated from sediment of a solar saltern pond in Gomso Bay, Republic of Korea. Comparative 16S rRNA gene sequence analysis showed that strains MK-B5T and MK-B7 belong to the
Gammaproteobacteria
and are related most closely to
Salinisphaera shabanensis
JCM 11575T ( = E1L3AT) (96.3 and 96.5 % similarity, respectively),
Salinisphaera dokdonensis
KCCM 90064T ( = CL-ES53T) (95.6 and 95.6 %) and
Salinisphaera hydrothermalis
JCM 115514T ( = EPR70T) (95.1 and 95.3 %). The level of 16S rRNA gene sequence similarity between strains MK-B5T and MK-B7 was 99.8 %. The G+C contents of their genomic DNAs were 63.4 and 63.6 mol%, respectively, and the major respiratory quinone was ubiquinone-8. DNA–DNA relatedness between strains MK-B5T and MK-B7 was 98 %, indicating that the two isolates represent a single species. However, the level of DNA–DNA relatedness between the two isolates and
S. shabanensis
E1L3AT (26.4–30.8 %) indicates that they represent a novel species. Strains MK-B5T and MK-B7 possessed C14 : 0, C16 : 0 and C19 : 0ω8c cyclo as major fatty acids. The two isolates were Gram-stain-negative, strictly aerobic, short rod-shaped and motile. They grew at 10–40 °C (optimum, 35–37 °C), at pH 5.0–8.5 (optimum, 7.0–7.5) and with 5–25 % (w/v) NaCl (optimum, 15 % NaCl). On the basis of phenotypic and phylogenetic analyses, strains MK-B5T and MK-B7 are thus considered to represent a novel species of the genus
Salinisphaera
, for which the name Salinisphaera orenii sp. nov. is proposed. The type strain is MK-B5T ( = KCTC 23198T = JCM 17073T).
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