Alternative biosynthetic starter units enhance the structural diversity of cyanobacterial lipopeptides

0505637 - BC 2020 RIV US eng J - Journal Article
Mareš, Jan - Hájek, J. - Urajová, P. - Kust, Andreja - Jokela, J. - Saurav, K. - Galica, T. - Čapková, Kateřina - Mattila, A. - Haapaniemi, E. - Permi, P. - Mysterud, I. - Skulberg, O.M. - Karlsen, J. - Fewer, D.P. - Sivonen, K. - Tonnesen, H.H. - Hrouzek, P.
Alternative biosynthetic starter units enhance the structural diversity of cyanobacterial lipopeptides.
Applied and Environmental Microbiology. Roč. 85, č. 4 (2019), č. článku e02675-18. ISSN 0099-2240. E-ISSN 1098-5336
R&D Projects: GA ČR(CZ) GA16-09381S
Institutional support: RVO:60077344
Keywords : biosynthesis * cyanobacteria * fatty acyl-AMP ligase * lipopeptides
OECD category: Microbiology
Impact factor: 4.016, year: 2019
Method of publishing: Open access
https://aem.asm.org/content/aem/85/4/e02675-18.full.pdf

Puwainaphycins (PUWs) and minutissamides (MINs) are structurally analogous cyclic lipopeptides possessing cytotoxic activity. Both types of compound exhibit high structural variability, particularly in the fatty acid (FA) moiety. Although a biosynthetic gene cluster responsible for synthesis of several PUW variants has been proposed in a cyanobacterial strain, the genetic background for MINs remains unexplored. Herein, we report PUW/MIN biosynthetic gene clusters and structural variants from six cyanobacterial strains. Comparison of biosynthetic gene clusters indicates a common origin of the PUW/MIN hybrid nonribosomal peptide synthetase and polyketide synthase. Surprisingly, the biosynthetic gene clusters encode two alternative biosynthetic starter modules, and analysis of structural variants suggests that initiation by each of the starter modules results in lipopeptides of differing lengths and FA substitutions. Among additional modifications of the FA chain, chlorination of minutissamide D was explained by the presence of a putative halogenase gene in the PUW/MIN gene cluster of Anabaena minutissima strain UTEX B 1613. We detected PUW variants bearing an acetyl substitution in Symplocastrum muelleri strain NIVA-CYA 644, consistent with an O-acetyltransferase gene in its biosynthetic gene cluster. The major lipopeptide variants did not exhibit any significant antibacterial activity, and only the PUW F variant was moderately active against yeast, consistent with previously published data suggesting that PUWs/MINs interact preferentially with eukaryotic plasma membranes.
Permanent Link: http://hdl.handle.net/11104/0297226