Bacterial type III polyketide synthases: phylogenetic analysis and potential for the production of novel secondary metabolites by heterologous expression in pseudomonads.
Type III polyketide synthases (PKS) were regarded as typical for plant secondary metabolism before they were found in microorganisms recently. Due to microbial genome sequencing efforts, more and more type III PKS are found, most of which of unknown function. In this manuscript, we report a comprehensive analysis of the phylogeny of bacterial type III PKS and report the expression of a type III PKS from the myxobacterium Sorangium cellulosum in pseudomonads. There is no precedent of a secondary metabolite that might be biosynthetically correlated to a type III PKS from any myxobacterium. Additionally, an inactivation mutant of the S. cellulosum gene shows no physiological difference compared to the wild-type strain which is why these type III PKS are assumed to be "silent" under the laboratory conditions administered. One type III PKS (SoceCHS1) was expressed in different Pseudomonas sp. after the heterologous expression in Escherichia coli failed. Cultures of recombinant Pseudomonas sp. harbouring SoceCHS1 turned red upon incubation and the diffusible pigment formed was identified as 2,5,7-trihydroxy-1,4-naphthoquinone, the autooxidation product of 1,3,6,8-tetrahydroxynaphthalene. The successful heterologous production of a secondary metabolite using a gene not expressed under administered laboratory conditions provides evidence for the usefulness of our approach to activate such secondary metabolite genes for the production of novel metabolites.
Gross
Frank
F
Institut für Pharmazeutische Biotechnologie, Universität des Saarlandes, Postfach 151150, 66041, Saarbrücken, Germany.
Luniak
Nora
N
Perlova
Olena
O
Gaitatzis
Nikolaos
N
Jenke-Kodama
Holger
H
Gerth
Klaus
K
Gottschalk
Daniela
D
Dittmann
Elke
E
Müller
Rolf
R
D000217:Acyltransferases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D009231:Myxococcales / Q000201:enzymology* / Q000235:genetics; D009285:Naphthoquinones / Q000737:chemistry; D010802:Phylogeny; D011549:Pseudomonas / Q000235:genetics
D009285:Naphthoquinones; C041659:flaviolin; D000217:Acyltransferases; C020141:flavanone synthetase