Edited by James M. Tiedje, Michigan State University, East Lansing, MI, and approved November 12, 2003 (received for review July 17, 2003)
Cyanobacteria are a prolific source of secondary metabolites, including compounds with toxic and enzyme-inhibiting activities. Microcystins and nodularins are the end products of a secondary metabolic pathway comprised of mixed polyketide synthases and nonribosomal peptide synthetases. Both peptides are potent natural toxins produced by distantly related genera of cyanobacteria. Horizontal gene transfer is thought to play a role in the sporadic distribution of microcystin producers among cyanobacteria. Our phylogenetic analyses indicate a coevolution of housekeeping genes and microcystin synthetase genes for the entire evolutionary history of the toxin. Hence they do not corroborate horizontal transfer of genes for microcystin biosynthesis between the genera. The sporadic distribution of microcystin synthetase genes in modern cyanobacteria suggests that the ability to produce the toxin has been lost repeatedly in the more derived lineages of cyanobacteria. The data we present here strongly suggest that the genes encoding nodularin synthetase are recently derived from those encoding microcystin synthetase.
↵ ∥ To whom correspondence should be addressed. E-mail: kaarina.sivonen{at}helsinki.fi.
↵ ‡ A.R. and D.P.F. contributed equally to this work.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database [accession nos. AJ515451–AJ515466, AJ515468–AJ515475 (mcyA), AY382530–AY382556 (mcyE), AY424980–AY424994 (mcyD), AY424995–AY4225003 (rpoC1), and AY439281–AY439283 (16S rRNA)].
