title: An Amidinohydrolase Provides the Missing Link in the Biosynthesis of Amino Marginolactone Antibiotics.
abstract: Desertomycin A is an aminopolyol polyketide containing a macrolactone ring. We have proposed that desertomycin A and similar compounds (marginolactones) are formed by polyketide synthases primed not with γ-aminobutanoyl-CoA but with 4-guanidinylbutanoyl-CoA, to avoid facile cyclization of the starter unit. This hypothesis requires that there be a final-stage de-amidination of the corresponding guanidino-substituted natural product, but no enzyme for such a process has been described. We have now identified candidate amidinohydrolase genes within the desertomycin and primycin clusters. Deletion of the putative desertomycin amidinohydrolase gene dstH in Streptomyces macronensis led to the accumulation of desertomycin B, the guanidino form of the antibiotic. Also, purified DstH efficiently catalyzed the in vitro conversion of desertomycin B into the A form. Hence this amidinohydrolase furnishes the missing link in this proposed naturally evolved example of protective-group chemistry.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
authors.forename: Markiyan
authors.initials: M
authors.lastname: Samborskyy
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.|Institut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1 B, 30167, Hannover, Germany.
authors.forename: Frederick
authors.initials: F
authors.lastname: Lindner
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. pfl10@cam.ac.uk.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D018942:Macrolides / Q000378:metabolism*; D013058:Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D000581:Amidohydrolases
keywords: amidinohydrolases; biosynthesis; marginolactones; polyketide synthases; streptomyces