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Stimulation of polyketide metabolism in Streptomyces fradiae by tylosin and its glycosylated precursors

Fish, Steven Anthony and Cundliffe, Eric (1997) Stimulation of polyketide metabolism in Streptomyces fradiae by tylosin and its glycosylated precursors. Microbiology, 143. pp. 3871-3876. ISSN 1350-0872

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Abstract

Three glycosyltransferases are involved in tylosin biosynthesis in Streptomyces fradiae. The first sugar to be added to the polyketide aglycone (tylactone) is mycaminose and the gene encoding mycaminosyltransferase is orf2* (tylM2). However, targeted disruption of orf2* did not lead to the accumulation of tylactone under conditions that normally favour tylosin production; instead, the synthesis of tylactone was virtually abolished. This may, in part, have resulted from a polar effect on the expression of genes downstream of orf2*, particularly orf4* (ccr) which encodes crotonyl-CoA reductase, an enzyme that supplies 4-carbon extender units for polyketide metabolism However, that cannot be the entire explanation, since tylosin production was restored at about 10% of the wild-type level when orf2* was re-introduced into the disrupted strain. When glycosylated precursors of tylosin were fed to the disrupted strain, they were converted to tylosin, confirming that two of the three glycosyltransferase activities associated with tylosin biosynthesis were still intact. Interestingly, however, tyladone also accumulated under such conditions and, to a much lesser extent, when tylosin was added to similar fermentations. It is concluded that glycosylated macrolides exert a pronounced positive effect on polyketide metabolism in S. fradiae.

Item Type: Article
Journal or Publication Title: Microbiology
Uncontrolled Keywords: polyketide metabolism ; Streptomyces fradiae ; glycosyltransferase ; tylosin production
Subjects:
Departments: Faculty of Science and Technology > School of Computing & Communications
ID Code: 79373
Deposited By: ep_importer_pure
Deposited On: 06 May 2016 14:44
Refereed?: Yes
Published?: Published
Last Modified: 22 Nov 2017 23:47
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/79373

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