期刊
JOURNAL OF NATURAL PRODUCTS
卷 83, 期 11, 页码 3338-3346出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.0c00675
关键词
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资金
- National Key Research and Development Program of China [2018YFA0903200/2018YFA0903201]
- China Postdoctoral Science Foundation [2019M663192]
- National Natural Science Foundation of China [31761143016, 81925037, 31870032, 31670036]
- 111 Project of Ministry of Education of the People's Republic of China [B13038]
- Chang Jiang Scholars Program (Young Scholar) from the Ministry of Education of China
- National High-level Personnel of Special Support Program [2017RA2259]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2019B151502014]
- Science and Technology Planning Project of Guangdong Province [2020A0505100041]
- Guangdong Special Support Program [2016TX03R280]
- Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program [2017BT01Y036]
- K. C. Wong Education Foundation
4-Hydroxy pyridones are a class of fungi-derived polyketide-nonribosomal peptide products featuring a core of 4-hydroxy-2-pyridone which have a wide range of biological activities. Genome mining of in-house strains using polyketide synthase-nonribosomal peptide synthase as a query identified an endophyte Tolypocladium sp. 49Y, which possesses a potential 4-hydroxy pyridone biosynthetic gene cluster. Heterologous expression in Aspergillus oryzae NSAR1 revealed that this gene cluster is functional and able to produce a rare type of 4-hydroxy pyridones called tolypyridones (compounds 3 and 4). Tolypocladium sp. 49Y was grown in a variety of media which led to the isolation of six 4-hydroxy pyridones (5-10) and one pyrrolidone (11) from a rice culture, and compounds 3 and 9 showed antifungal activity. These latter compounds are different from those obtained by heterologous expression. This study shows that both heterologous expression and cultivation of the native host are complementary approaches to discover new natural products.
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