Rice blast disease, caused by Magnaporthe oryzae, is the most devastating cereal killer worldwide. Note that melanin pigment is an essential factor of M. oryzae virulence, thus fungicides interfering with melanin biosynthesizing enzymes would reduce the pathogenicity. Scytalone dehydratase (SDH) is the key target for commercial fungicides, like carpropamid, due to its role in the dehydration reaction of the fungal melanin pathway. However, a single-point mutation (V75M) in SDH elicits resistance to carpropamid. A lack of effective fungicides against this resistant strain expedited the quest for novel bioactive inhibitors. Currently, bacterial endophytes like Streptomyces have been heralded for synthesizing bioactive metabolites to protect plants from phytopathogens. The literature search led to the identification of 21 Streptomyces spp. symbionts of paddy that can suppress M. oryzae growth. An antiSMASH server was used to explore Streptomyces spp. gene clusters and found 4463 putative metabolites. Besides, 745 unique metabolites were subjected to a series of virtual screening techniques. Ideally, this process identified five potential SDH inhibitors. The docking result highlights that the metabolite pseudopyronine A interacted hydrophobically with both Val75 of SDH^WT and Met75 of SDH^V75M targets. Moreover, pseudopyronine A has a higher binding free energy with SDH^WT (- 89.94 kcal/mol) and SDH^V75M (- 71.95 kcal/mol). Interestingly, the pyranones scaffold of pseudopyronine A was reported for antifungal activity against phytopathogens. Dynamic behavior confirms that pseudopyronine A has excellent conformational states with both SDH^WT and SDH^V75M. Altogether, we hope that this study creates a new avenue for the discovery of novel phytopathogen inhibitors from endophytes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13205-023-03859-7.

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Indication	Highest Phase	Country/Location	Organization	Date
Atherosclerosis	Preclinical	JP	Kitasato University	11 May 2016

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