Examination of Substrate Specificity of the First Adenylation Domain in mcyA Module Involved in Microcystin Biosynthesis

Authors : Gözde YAMAN, Mete YILMAZ

Pages : 275-285

Doi:10.21448/ijsm.715530

View : 10 | Download : 10

Publication Date : 2020-12-15

Article Type : Research Paper

Abstract :The cyanotoxin microcystin insert ignore into journalissuearticles values(MC); is a secondary metabolite, synthesized by nonribosomal peptide synthetase insert ignore into journalissuearticles values(NRPS); and polyketide synthase insert ignore into journalissuearticles values(PKS); enzymes. It has many isoforms and the mechanism of its diversity is not well understood. One of the MC synthetase genes, mcyA, codes for the McyA module containing two adenylation insert ignore into journalissuearticles values(A); domains. The first domain, McyA-A1, generally binds to L-serine insert ignore into journalissuearticles values(L-ser);. Then the N-methyl transferase insert ignore into journalissuearticles values(NMT); domain converts L-Ser into N-methyldehydroalanine insert ignore into journalissuearticles values(Mdha);, which usually occupies position 7 on the MC molecule. However, various other amino acids insert ignore into journalissuearticles values(AAs); might also be present at this position. In this study, bioinformatic analyses of selected cyanobacteria were performed to understand whether genetic information in the first adenylation domain of mcyA could explain incorporation of different AAs at position 7 of the MC molecule. Binding pocket signatures of McyA-A1 and putative activated AAs were determined via various bioinformatics tools. Maximum likelihood phylogenetic trees of full length mcyA, mcyA-A1 and 16S rRNA genes were prepared in Mega 6. Phylogenetic analysis of mcyA-A1 nucleotide sequences was in agreement with the predictions of activated AAs by McyA-A1. In comparison with the 16S rRNA and full length mcyA gene trees, mcyA-A1 phylogenetic trees suggested horizontal transfer of the A domain in either Planktothrix agardhii insert ignore into journalissuearticles values(Gomont); Anagnostidis & Komárek or Planktothrix rubescens insert ignore into journalissuearticles values(De Candolle ex Gomont); Anagnostidis & Komárek strains. Predictions of activated AAs were generally in agreement with the chemically determined position 7 AAs. However, there were exceptions suggesting the multispecificity of the first A domain of McyA in some cyanobacteria.
Keywords : Microcystin, Nonribosomal Peptides, Polyketide Synthase, Adenylation Domain, Bioinformatics