Expression of pyrrothine N-acyltransferase activities in Saccharothrix algeriensis NRRL B-24137: new insights into dithiolopyrrolone antibiotic biosynthetic pathway.

ABSTRACT

AIMS: The hypothetical dithiolopyrrolone biosynthetic pathway includes a final step of pyrrothine nucleus acylation. The presence of an enzymatic activity catalysing this reaction was investigated in Saccharothrix algeriensis NRRL B-24137. To understand the effect exerted by organic acids on the level of dithiolopyrrolone production, their influence on enzymatic expression was studied. METHODS AND RESULTS: The transfer of acetyl-CoA or benzoyl-CoA on pyrrothine was assayed in the cell-free extract of Sa. algeriensis NRRL B-24137. This study reports the presence of an enzymatic activity catalysing this reaction that was identified as either pyrrothine N-acetyltransferase or N-benzoyltransferase. The stimulation of benzoyl-pyrrothine (BEP) production by addition of benzoic acid at 1.25 mmol l(-1) into the culture medium was demonstrated, and results showed that under the same conditions of growth, pyrrothine N-benzoyltransferase specific activity was doubled. CONCLUSIONS: This study shows that BEP production is enhanced in the presence of benzoic acid partly because of an induction of pyrrothine N-benzoyltransferase. SIGNIFICANCE AND IMPACT OF THE STUDY The antitumor and antibiotic properties of dithiolopyrrolones are related to their variable acyl groups. New insights into regulation of biosynthetic pathway, especially the step of pyrrothine acylation, could lead after further studies to yield improvement and to selective production of dithiolopyrrolones with new biological activities.