An acyl-coenzyme A carboxylase encoding gene associated with jadomycin biosynthesis in Streptomyces venezuelae ISP5230

Analysis of a region of chromosomal DNA lying between jadR(1) and jadI in t he gene cluster for jadomycin biosynthesis in Streptomyces venezuelae ISP52 30 detected an ORF encoding 584 amino acids similar in sequence to the biot in carboxylase (BC) and biotin carboxyl carrier protein (BCCP) components o f acyl-coenzyme A carboxylases, Multiple sequence alignments of the deduced Jad protein with acyl-coenzyme A carboxylases from various sources located the DC and BCCP components in the N- and C-terminal regions, respectively, of the deduced polypeptides. The organization and amino acid sequence of t he deduced polypeptide most closely resembled those in other Gram-positive bacteria broadly classified as actinomycetes. Disrupting the gene, designat ed jadJ, severely reduced but did not eliminate jadomycin production. The d isruption had no effect on growth or morphology of the organism, implying t hat the product of jadJ is not essential for fatty acid biosynthesis, It is concluded that jadJ supplies malonyl-coenzyme A for biosynthesis of the po lyketide intermediate that is eventually processed to form the antibiotic j adomycin B.