1887

Abstract

Eight additional genes, , , , , , , and , in the cluster of ISP5230, were located immediately downstream of by chromosome walking. Sequence analyses and comparisons implicated them in biosynthesis of the 2,6-dideoxysugar in jadomycin B. The genes were cloned in , inactivated by inserting an apramycin resistance cassette with a promoter driving transcription of downstream genes, and transferred into by intergeneric conjugation. Analysis by HPLC and NMR of intermediates accumulated by cultures of the insertionally inactivated mutants indicated that , , , , , and mediate formation of the dideoxysugar moiety of jadomycin B and its attachment to the aglycone. Based on these results and sequence similarities to genes described in other species producing deoxysugar derivatives, a biosynthetic pathway is proposed in which the product (glucose-1-phosphate nucleotidyltransferase) activates glucose to its nucleotide diphosphate (NDP) derivative, and the product (a 4,6-dehydratase) converts this to NDP-4-keto-6-deoxy-D-glucose. An NDP-hexose 2,3-dehydratase and an oxidoreductase, encoded by and , respectively, catalyse ensuing reactions that produce an NDP-2,6-dideoxy-D--4-hexulose. The product of (NDP-4-keto-2,6-dideoxy-5-epimerase) converts this intermediate to its L- form and the product (NDP-4-keto-2,6-dideoxyhexose 4-ketoreductase) reduces the keto group of the NDP-4-hexulose to give an activated form of the L-digitoxose moiety in jadomycin B. Finally, a glycosyltransferase encoded by transfers the activated sugar to jadomycin aglycone. The function of is unclear; the gene is not essential for jadomycin B biosynthesis, but its presence ensures complete conversion of the aglycone to the glycoside. The deduced amino acid sequence of a 612 bp ORF (*) downstream of the dideoxysugar biosynthesis genes resembles many TetR-family transcriptional regulator sequences.

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2002-04-01
2019-10-21
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