TY - JOUR
T1 - A PKS/NRPS/FAS Hybrid Gene Cluster from Serratia plymuthica RVH1 Encoding the Biosynthesis of Three Broad Spectrum, Zeamine-Related Antibiotics
AU - Masschelein, Joleen
AU - Mattheus, Wesley
AU - Gao, Ling-Jie
AU - Moons, Pieter
AU - Van Houdt, Rob
AU - Uytterhoeven, Birgit
AU - Lamberigts, Chris
AU - Lescinier, Eveline
AU - Rozenski, Jef
AU - Herdewijn, Piet
AU - Aertsen, Abram
AU - Michiels, Chris
AU - Lavigne, Rob
N1 - Score = 10
PY - 2013/1/17
Y1 - 2013/1/17
N2 - 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.
AB - 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.
KW - antibiotics
KW - quorum sensing
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/ezp_127010
UR - http://knowledgecentre.sckcen.be/so2/bibref/9961
U2 - 10.1371/journal.pone.0054143
DO - 10.1371/journal.pone.0054143
M3 - Article
SN - 1932-6203
VL - 8
SP - 54143
EP - 54143
JO - PLOS ONE
JF - PLOS ONE
IS - 1
ER -