Browse by author
Lookup NU author(s): Professor Michael Goodfellow
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
The antibiotics lactonamycin and lactonamycin Z provide attractive leads for antibacterial drug development. Both antibiotics contain a novel aglycone core called lactonamycinone. To gain insight into lactonamycinone biosynthesis, cloning and precursor incorporation experiments were undertaken. The lactonamycin gene cluster was initially cloned from Streptomyces rishiriensis. Sequencing of ca. 61 kb of S. rishiriensis DNA revealed the presence of 57 open reading frames. These included genes coding for the biosynthesis of L-rhodinose, the sugar found in lactonamycin, and genes similar to those in the tetracenomycin biosynthetic gene cluster. Since lactonamycin production by S. rishiriensis could not be sustained, additional proof for the identity of the S. rishiriensis cluster was obtained by cloning the lactonamycin Z gene cluster from Streptomyces sanglieri. Partial sequencing of the S. sanglieri cluster revealed 15 genes that exhibited a very high degree of similarity to genes within the lactonamycin cluster, as well as an identical organization. Double-crossover disruption of one gene in the S. sanglieri cluster abolished lactonamycin Z production, and production was restored by complementation. These results confirm the identity of the genetic locus cloned from S. sanglieri and indicate that the highly similar locus in S. rishiriensis encodes lactonamycin biosynthetic genes. Precursor incorporation experiments with S. sanglieri revealed that lactonamycinone is biosynthesized in an unusual manner whereby glycine or a glycine derivative serves as a starter unit that is extended by nine acetate units. Analysis of the gene clusters and of the precursor incorporation data suggested a hypothetical scheme for lactonamycinone biosynthesis. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Author(s): Zhang X, Alemany LB, Fiedler H-P, Goodfellow M, Parry RJ
Publication type: Article
Publication status: Published
Journal: Antimicrobial Agents and Chemotherapy
Year: 2008
Volume: 52
Issue: 2
Pages: 574-585
ISSN (print): 0066-4804
ISSN (electronic): 1098-6596
Publisher: American Society for Microbiology
URL: http://dx.doi.org/10.1128/AAC.00717-07
DOI: 10.1128/AAC.00717-07
PubMed id: 18070976
Altmetrics provided by Altmetric
