1887

Abstract

Hybridizing fragments in the genomic DNA of ISP5230, which produces the jadomycin group of angucycline antibiotics, were detected by probing with DNA from A3(2). The hybridizing regions were isolated from a 16.5 kb insert of λ replacement vector. Subcloning and sequencing of a 4.8 kb segment of the insert, containing regions hybridizing to as well as , identified five open reading frames (ORFs). The deduced polypeptide products of the ORFs closely resemble in sequence the components of streptomycete type-II polyketide synthases (PKSs): the ORF1 product corresponds to the ketoacyl synthase, and the ORF2 product to a polypeptide closely related to the ketoacyl synthase and involved in determining chain length; the ORF3 product matches the acyl carrier protein; ORF4 encodes a bifunctional cyclase/dehydrase; and ORF5 encodes a ketoreductase. Integration into the chromosomal DNA of a plasmid containing a segment of the ORF2-ORF4 region severely depressed jadomycin B biosynthesis; since the integrant showed no change in growth or spore pigmentation, the cloned PKS genes are presumed to encode enzymes in the pathway for jadomycin biosynthesis.

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1994-12-01
2021-10-21
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