Scopularide A is a promising potent anticancer lipopeptide isolated from a marine derived Scopulariopsis brevicaulis strain. The compound consists of a reduced carbon chain (3-hydroxy-methyldecanoyl) attached to five amino acids (glycine, l-valine, d-leucine, l-alanine, and l-phenylalanine). Using the newly sequenced S. brevicaulis genome we were able to identify the putative biosynthetic gene cluster using genetic information from the structurally related emericellamide A from Aspergillus nidulans and W493-B from Fusarium pseudograminearum. The scopularide A gene cluster includes a nonribosomal peptide synthetase (NRPS1), a polyketide synthase (PKS2), a CoA ligase, an acyltransferase, and a transcription factor. Homologous recombination was low in S. brevicaulis so the local transcription factor was integrated randomly under a constitutive promoter, which led to a three to four-fold increase in scopularide A production. This indirectly verifies the identity of the proposed biosynthetic gene cluster.
- non-ribosomal peptide synthetases
- polyketide synthases
- secondary metabolites
- transcription factor
- marine fungi
Lukassen, M. B., Saei, W., Sondergaard, T. E., Tamminen, A., Kumar, A., Kempken, F., Wiebe, M. G., & Sørensen, J. L. (2015). Identification of the scopularide biosynthetic gene cluster in Scopulariopsis brevicaulis. Marine Drugs, 13(7), 4331-4343. https://doi.org/10.3390/md13074331