Genetic analysis of polyketide synthase and peptide synthetase genes in cyanobacteria as a mining tool for secondary metabolites

• Published in: Journal of industrial microbiology & biotechnology 2007-06, Vol.34 (6), p.443-456
• Main Authors: Barrios-Llerena, Martin E, Burja, Adam M, Wright, Phillip C
• Format: Article
• Language: English
• Subjects: Adenylation; Amino acids; Binding; Biological and medical sciences; Biosynthesis; Biotechnology; Biotechnology - methods; Chroococcales; Cyanobacteria; Cyanobacteria - classification; Cyanobacteria - enzymology; Cyanobacteria - genetics; Cyanobacteria - metabolism; Depsipeptides - chemistry; Depsipeptides - metabolism; Domains; Fundamental and applied biological sciences. Psychology; Genes; Genetic analysis; Metabolites; Modules; Molecular Sequence Data; Natural products; Nostocales; Oscillatoriales; Peptide Synthases - genetics; Peptide Synthases - metabolism; peptide synthetase; Peptides, Cyclic - chemistry; Peptides, Cyclic - metabolism; Polyketide synthase; Polyketide Synthases - genetics; Polyketide Synthases - metabolism; Polymerase Chain Reaction; Proteobacteria; Scytonema; Secondary metabolites; Sequence Analysis, DNA; Structure-Activity Relationship; Structure-function relationships
• ISSN: 1367-5435; 1476-5535
• DOI: 10.1007/s10295-007-0216-6

Molecular screening using degenerate PCR to determine the presence of secondary metabolite genes in cyanobacteria was performed. This revealed 18 NRPS and 19 PKS genes in the 21 new cyanobacterial strains examined, representing three families of cyanobacteria (Nostocales, Chroococales and Oscillatoriales). A BLAST analysis shows that these genes have similarities to known cyanobacterial natural products. Analysis of the NRPS adenylation domain indicates the presence of novel features previously ascribed to both proteobacteria and cyanobacteria. Furthermore, binding-pocket predictions reveal diversity in the amino acids used during the biosynthesis of compounds. A similar analysis of the PKS ketosynthase domain shows significant structural diversity and their presence in both mixed modules with NRPS domains and individually as part of a PKS module. We have been able to classify the NRPS genes on the basis of their binding-pockets. Further, we show how this data can be used to begin to link structure to function by an analysis of the compounds Scyptolin A and Hofmannolin from Scytonema sp. PCC 7110.