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A novel 20-membered ester-incorporating benzenoid ansamycin, phenolmacrolide A (1), and a new naphthalenoid ansamycin, olimycin I (2), were obtained from the marine-derived Streptomyces olivaceus NBUA17 using a strategy of combining genome mining, SNAP-MS, and HSQC NMR interpretation tools. Furthermore, investigation of the putative ansamycin biosynthetic gene cluster suggested that the novel benzenoid ansamycin scaffold of compound 1 could be formed in part by a hydroxylase and luciferase-like monooxygenase. Compound 1 exhibited moderate activity inhibiting proliferation, migration, and invasion against PANC-1 cells in vitro by inducing cell apoptosis and promoting cancer cell entry into G2\/M phase, and inhibiting epithelial-mesenchymal transition. Further drug affinity-responsive target stability assay, molecular docking, cell thermal shift assay, and siRNA transfection identified EEF1A2 as a molecular target of compound 1 in PANC-1 cells. 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Enrico H.","family":"Lazaro","sequence":"additional","affiliation":[{"name":"University of the Philippines Diliman , , ,","place":["Quezon, Philippines, 1101"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4978-4083","authenticated-orcid":true,"given":"Wenhan","family":"Lin","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Ningbo, China, 315800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-506X","authenticated-orcid":true,"given":"C. 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