A1 Refereed original research article in a scientific journal
HYBRID ANTHRACYCLINE ANTIBIOTICS - PRODUCTION OF NEW ANTHRACYCLINES BY CLONED GENES FROM STREPTOMYCES-PURPURASCENS IN STREPTOMYCES-GALILAEUS
Authors: NIEMI J, YLIHONKO K, HAKALA J, PARSSINEN R, KOPIO A, MANTSALA P
Publisher: SOC GENERAL MICROBIOLOGY
Publication year: 1994
Journal:: Microbiology
Journal name in source: MICROBIOLOGY-UK
Journal acronym: MICROBIOL-UK
Volume: 140
First page : 1351
Last page: 1358
Number of pages: 8
ISSN: 1350-0872
DOI: https://doi.org/10.1099/00221287-140-6-1351
Abstract
A DNA segment cloned from Streptomyces purpurascens ATCC 25489 close to a region that hybridized to a probe containing part of the adinorhodin polyketide synthase caused S. galilaeus ATCC 31615 to produce new anthracyclines. When transformed with certain sub-clones of this segment, the host produced glycosides of epsilon-rhodomycinone, beta-rhodomycinone, 10-demethoxycarbonylaklavinone and 11-deoxy-beta-rhodomycinone in addition to those of aklavinone, the natural anthracyclines of S. galilaeus. The first two compounds are S. purpurascens products and the other two are novel compounds that conceptually are structural hybrids between S. galilaeus and S. purpurascens products. Three glycosides of one of the novel aglycones, 11-deoxy-beta-rhodomycinone, were purified and found to possess cytotoxic activity against L1210 mouse leukaemia cells. Separate regions of the cloned S. purpurascens DNA are responsible for modification of the S. galilaeus host product at the 10- and 11-positions.
A DNA segment cloned from Streptomyces purpurascens ATCC 25489 close to a region that hybridized to a probe containing part of the adinorhodin polyketide synthase caused S. galilaeus ATCC 31615 to produce new anthracyclines. When transformed with certain sub-clones of this segment, the host produced glycosides of epsilon-rhodomycinone, beta-rhodomycinone, 10-demethoxycarbonylaklavinone and 11-deoxy-beta-rhodomycinone in addition to those of aklavinone, the natural anthracyclines of S. galilaeus. The first two compounds are S. purpurascens products and the other two are novel compounds that conceptually are structural hybrids between S. galilaeus and S. purpurascens products. Three glycosides of one of the novel aglycones, 11-deoxy-beta-rhodomycinone, were purified and found to possess cytotoxic activity against L1210 mouse leukaemia cells. Separate regions of the cloned S. purpurascens DNA are responsible for modification of the S. galilaeus host product at the 10- and 11-positions.
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