New Tetramic Acids Comprising of Decalin and Pyridones From SD-80A With Antimicrobial Activity.

Cycloaddition reactions such as intramolecular Diels-Alder (IMDA) are extremely important in constructing multicyclic scaffolds with diverse bioactivities. Using MycB as a biomarker, three new polyketides - Chaetolivacines A (), B (), and C () - with one known compound Myceliothermophin E () comprising of decalin and 4-hydroxy-2-pyridones were obtained from the culture of SD-80A under the guidance of gene mining. The structures of these compounds were established using detailed 1D, 2D NMR, and high-resolution electron spray ionization mass spectroscopy (HRESIMS) analysis. The relative and absolute configurations of the compounds , , and were elucidated by NOESY and ECD. The biosynthesis pathways of these compounds were proposed, which involves in three key genes [polyketide synthase-non-ribosomal peptide synthetases (PKS-NRPS)], , and . Compounds - were tested for their antimicrobial activities, and compounds and showed moderate bioactivity against (SA) and methicillin-resistant (MRSA) with MIC values of 15.8 and 27.1 μM. The results showed that configuration of C-21 in and is important for anti-SA and anti-MRSA activities. This study reveals the significant potential of the genus in producing new PKS-NRPS, therefore increasing the speed in the mining for new sources of antimicrobial agents.