A tailoring activity is responsible for generating polyene amide derivatives in Streptomyces diastaticus var. 108.
We recently characterized rimocidin B (3b) and CE-108B (4b) as two polyene amides with improved pharmacological properties, produced by genetically modified Streptomyces diastaticus var. 108. In this work, genetic and biochemical analysis of the producer strain show that the two amides are derived from the parental polyenes rimocidin (3a) and CE-108 (4a) by a post-PKS modification of the free side chain carboxylic acid. This modification is mediated by an amidotransferase activity operating after the biosynthesis of rimocidin (3a) and CE-108 (4a) are completed. Two polyenes, intermediates of the biosynthetic pathway of rimocidin (3a) and CE-108 (4a), were also isolated and shown to have some improved pharmacological properties compared with the final products.
Seco
Elena M
EM
Centro Nacional de Biotecnología, Campus de la Universidad Autónoma de Madrid, Cantoblanco, Spain.
Fotso
Serge
S
Laatsch
Hartmut
H
Malpartida
Francisco
F
D000577:Amides / Q000145:classification / Q000378:metabolism*; D006462:Hemolytic Plaque Technique; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000145:classification / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009005:Monosaccharides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009154:Mutation; D011090:Polyenes / Q000737:chemistry / Q000145:classification / Q000378:metabolism* / Q000494:pharmacology; D013302:Streptomyces / Q000145:classification / Q000235:genetics* / Q000378:metabolism
D000577:Amides; C485858:CE-108; D018942:Macrolides; D009005:Monosaccharides; D011090:Polyenes; C003273:rimocidin