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

Abstract

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>1</b>), B (<b>3</b>), and C (<b>4</b>) - with one known compound Myceliothermophin E (<b>2</b>) comprising of decalin and 4-hydroxy-2-pyridones were obtained from the culture of <i>Chaetomium olivaceum</i> 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 <b>1</b>, <b>3</b>, and <b>4</b> were elucidated by NOESY and ECD. The biosynthesis pathways of these compounds were proposed, which involves in three key genes <i>ChaA</i> [polyketide synthase-non-ribosomal peptide synthetases (PKS-NRPS)], <i>ChaB</i>, and <i>ChaC</i>. Compounds <b>1</b>-<b>4</b> were tested for their antimicrobial activities, and compounds <b>2</b> and <b>3</b> showed moderate bioactivity against <i>Staphylococcus aureus</i> (SA) and methicillin-resistant <i>S. aureus</i> (MRSA) with MIC values of 15.8 and 27.1 μM. The results showed that configuration of C-21 in <b>3</b> and <b>4</b> is important for anti-SA and anti-MRSA activities. This study reveals the significant potential of the genus <i>Chaetomium</i> in producing new PKS-NRPS, therefore increasing the speed in the mining for new sources of antimicrobial agents.