30 / 2021-10-09 15:55:33

16-Residue Peptaibols from the Sponge-derived Acremonium sp. IMB18-086 Co-cultivated with Autoclaved Pseudomonas aeruginosa.

Co-cultivation；antimicrobials；peptaibols；sponge-associated fungus

It is well known that many biosynthetic gene clusters in microorganisms remain silent under standard laboratory conditions. Co-culturing different microbes in a single environment is one of the effective approaches to enhance the chemical diversity of metabolites.¹ Co-cultivation can create a competitive environment, which may activate the silent secondary metabolism genes and lead to the biosynthesis of bioactive products responsible for chemical defense.² An increasing number of co-culture experiments have led to discover new antimicrobials or enhance the accumulation of metabolites even in the absence of viable bacterial cells. As a part of our ongoing search for new antimicrobials,^{3, 4} we screened the sponge-derived microbes by co-culturing with different microbes, including bacteria, actinomycetes, and fungi. In our preliminary experiment, the co-cultures of the sponge-associated fungus Acremonium sp. IMB18-086 with the autoclaved bacterium Pseudomonas aeruginosa on the solid rice media showed enhanced antimicrobial activity. LC-MS analysis further revealed the presence of several newly induced metabolites and an prominent up to 20-fold increase of the accumulation of constitutively present fungal metabolites in comparison with the pure axenic cultures. Further chemical investigation afforded six new antimicrobial peptaibols, acremopeptaibols A-F (1-6), along with five known compounds, were isolated from the co-cultures of the sponge-associated fungus Acremonium sp. IMB18-086 with the autoclaved bacterium Pseudomonas aeruginosa on solid rice medium. Compounds 1-6 were featured by the lack of the highly conserved Thr⁶ and Hyp¹⁰ residues in comparison with other members of the SF3 subfamily peptaibols. A plausible biosynthetic pathway of compounds 1-6 was proposed on the basis of genomic analysis. Compounds 1 and 5 exhibited significant antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Candida albicans.