Bioactive secondary metabolites produced by fungi of the genus Diaporthe (Phomopsis): Structures, biological activities, and biosynthesis

Diaporthe and its anamorph Phomopsis, a genus of endophytic, saprotrophic, and plant pathogenic fungi, are found in many different ecosystems worldwide. Diaporthe (Phomopsis) fungi generate natural products such as pyrones, polyketides, alkaloids, and terpenoids. Most of these natural products show antibacterial, anti-inflammatory, and/or cytotoxic activity. In this review, we describe the 331 bioactive secondary metabolites isolated from 75 known species and various unidentified species of Diaporthe and Phomopsis from 2016 to 2021. These products comprise 143 bioactive compounds from Diaporthe and 188 from Phomopsis, including quinones, alkaloids, terpenoids, pyrones, polyketides, diphenyl ketones, diphenyl ethers, steroids, and fatty acids. The major activities of these compounds are as cytotoxic, antibacterial, and anti-inflammatory chemicals. All 21 fungi in the genus Diaporthe (Phomopsis) with available whole genome sequencing data contain several gene clusters for secondary metabolite biosynthesis. Such gene clusters and biosynthetic mechanisms have been identified for rugulosin A, terpestacin, and sch-642305. Diaporthe (Phomopsis) fungi produce abundant novel active natural products with great potential for drug development. In addition, these fungi provide important resources for research on the biosynthesis of secondary metabolites.