AUTHOR=Wang Xinzhu , Zhao Liya , Liu Chao , Qi Jun , Zhao Peipei , Liu Zhaoming , Li Chunlei , Hu Yingying , Yin Xin , Liu Xin , Liao Zhixin , Zhang Lixin , Xia Xuekui 

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

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02958

DOI=10.3389/fmicb.2019.02958

ISSN=1664-302X

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