AUTHOR=Dewapriya Pradeep , Khalil Zeinab G. , Prasad Pritesh , Salim Angela A. , Cruz-Morales Pablo , Marcellin Esteban , Capon Robert J. 

TITLE=Talaropeptides A-D: Structure and Biosynthesis of Extensively N-methylated Linear Peptides From an Australian Marine Tunicate-Derived Talaromyces sp.

JOURNAL=Frontiers in Chemistry

VOLUME=6

YEAR=2018

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2018.00394

DOI=10.3389/fchem.2018.00394

ISSN=2296-2646

ABSTRACT=<p>An Australian marine tunicate-derived fungus, <italic>Talaromyces</italic> sp. CMB-TU011 was subjected to a program of analytical microbioreactor (MATRIX) cultivations, supported by UHPLC-QTOF profiling, to reveal conditions for producing a new class of extensively <italic>N</italic>-methylated 11-12 residue linear peptides, talaropeptides A-D (<bold>2</bold>-<bold>5</bold>). The structures for <bold>2</bold>-<bold>5</bold>, inclusive of absolute configurations, were determined by a combination of detailed spectroscopic and chemical (e.g., C<sub>3</sub> and C<sub>18</sub> Marfey's) analyses. We report on the biological properties of <bold>2</bold>-<bold>5</bold>, including plasma stability, as well as antibacterial, antifungal and cell cytotoxicity. The talaropeptide mega non-ribosomal peptide synthetase (NRPS) is described, as second only in size to that for the fungus-derived immunosuppressant cyclosporine (an 11-residue extensively <italic>N</italic>-methylated cyclic peptide).</p>