A PKS/NRPS/FAS Hybrid Gene Cluster from Serratia plymuthica RVH1 Encoding the Biosynthesis of Three Broad Spectrum,Zeamine-Related Antibiotics |
| |
Authors: | Joleen Masschelein Wesley Mattheus Ling-Jie Gao Pieter Moons Rob Van Houdt Birgit Uytterhoeven Chris Lamberigts Eveline Lescrinier Jef Rozenski Piet Herdewijn Abram Aertsen Chris Michiels Rob Lavigne |
| |
Affiliation: | 1. Division of Gene Technology, KU Leuven, Heverlee, Belgium.; 2. Laboratory of Food Microbiology, KU Leuven, Heverlee, Belgium.; 3. Interface Valorisation Platform, KU Leuven, Leuven, Belgium.; 4. Laboratory for Medicinal Chemistry, Rega Institute for Medicinal Research, Leuven, Belgium.; University of Groningen, The Netherlands, |
| |
Abstract: | Serratia plymuthica strain RVH1, initially isolated from an industrial food processing environment, displays potent antimicrobial activity towards a broad spectrum of Gram-positive and Gram-negative bacterial pathogens. Isolation and subsequent structure determination of bioactive molecules led to the identification of two polyamino antibiotics with the same molecular structure as zeamine and zeamine II as well as a third, closely related analogue, designated zeamine I. The gene cluster encoding the biosynthesis of the zeamine antibiotics was cloned and sequenced and shown to encode FAS, PKS as well as NRPS related enzymes in addition to putative tailoring and export enzymes. Interestingly, several genes show strong homology to the pfa cluster of genes involved in the biosynthesis of long chain polyunsaturated fatty acids in marine bacteria. We postulate that a mixed FAS/PKS and a hybrid NRPS/PKS assembly line each synthesize parts of the backbone that are linked together post-assembly in the case of zeamine and zeamine I. This interaction reflects a unique interplay between secondary lipid and secondary metabolite biosynthesis. Most likely, the zeamine antibiotics are produced as prodrugs that undergo activation in which a nonribosomal peptide sequence is cleaved off. |
| |
Keywords: | |
|
|