Antifungal activity improved by coproduction of cyclodextrins and anabaenolysins in Cyanobacteria.

Abstract:

:Cyclodextrins are cyclic oligosaccharides widely used in the pharmaceutical industry to improve drug delivery and to increase the solubility of hydrophobic compounds. Anabaenolysins are lipopeptides produced by cyanobacteria with potent lytic activity in cholesterol-containing membranes. Here, we identified the 23- to 24-kb gene clusters responsible for the production of the lipopeptide anabaenolysin. The hybrid nonribosomal peptide synthetase and polyketide synthase biosynthetic gene cluster is encoded in the genomes of three anabaenolysin-producing strains of Anabaena. We detected previously unidentified strains producing known anabaenolysins A and B and discovered the production of new variants of anabaenolysins C and D. Bioassays demonstrated that anabaenolysins have weak antifungal activity against Candida albicans. Surprisingly, addition of the hydrophilic fraction of the whole-cell extracts increased the antifungal activity of the hydrophobic anabaenolysins. The fraction contained compounds identified by NMR as α-, β-, and γ-cyclodextrins, which undergo acetylation. Cyclodextrins have been used for decades to improve the solubility and bioavailability of many drugs including antifungal compounds. This study shows a natural example of cyclodextrins improving the solubility and efficacy of an antifungal compound in an ancient lineage of photosynthetic bacteria.

authors

Shishido TK,Jokela J,Kolehmainen CT,Fewer DP,Wahlsten M,Wang H,Rouhiainen L,Rizzi E,De Bellis G,Permi P,Sivonen K

doi

10.1073/pnas.1510432112

subject

Has Abstract

pub_date

2015-11-03 00:00:00

pages

13669-74

issue

44

eissn

0027-8424

issn

1091-6490

pii

1510432112

journal_volume

112

pub_type

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