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Download fileCytotoxic Anthracycline Metabolites from a Recombinant Streptomyces
journal contribution
posted on 2018-05-16, 16:07 authored by Chun Gui, Jie Yuan, Xuhua Mo, Hongbo Huang, Shanwen Zhang, Yu-Cheng Gu, Jianhua JuThe C7 (C9 or C10)-O-l-rhodosamine-bearing
anthracycline antibiotic cytorhodins and their biosynthetic intermediates
were recently isolated from Streptomyces sp. SCSIO
1666. Cosmid p17C4 from the Streptomyces lydicus genomic
library, which harbors both the biosynthetic genes for l-rhodinose (or 2-deoxy-l-fucose) and its glycosyltransferase
(encoded by slgG), was introduced into SCSIO 1666 to yield the recombinant
strain Streptomyces sp. SCSIO 1666/17C4. Chemical
investigations of this strain’s secondary metabolic potential
revealed the production of different anthracyclines featuring C7-O-l-rhodinose (or 2-deoxy-l-fucose) instead
of the typically observed l-rhodosamine. Purification of
the fermentation broth yielded 12 new anthracycline antibiotics including
three new ε-rhodomycinone derivatives, 1, 4, and 8, nine new β-rhodomycinone derivatives, 2, 3, 5–7, and 9–12, and three known compounds, l-rhodinose-l-rhodinose-l-rhodinoserhodomycinone
(13), ε-rhodomycinone (14), and γ-rhodomycinone
(15). All compounds were characterized on the basis of
detailed spectroscopic analyses and comparisons with previously reported
data. These compounds exhibited cytotoxicity against a panel of human
cancer cell lines. Significantly, compounds 4 and 13 displayed pronounced activity against HCT-116 as characterized
by IC50 values of 0.3 and 0.2 μM, respectively; these
IC50 values are comparable to that of the positive control
epirubicin.
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2- deoxy-l-fucosebiosyntheticcompoundIC 50 valuesHCTSCSIO 1666. Cosmid p 17Cstrain Streptomyces spε- rhodomycinone derivativesStreptomyces lydicus genomic libraryl-rhodinosel-rhodosamine-bearing anthracycline antibiotic cytorhodinscancer cell lines0.2 μ MCytotoxic Anthracycline Metabolitesβ- rhodomycinone derivativesC 7- O