Nine new (<b>1</b>-<b>3</b>, <b>5</b>-<b>8</b>, <b>11</b>, and <b>12</b>; named filipins VI-XIV) and three known (<b>4</b>, <b>9</b>, and <b>10</b>) filipin-type polyene macrolides were isolated from the deep-sea-derived <i>Streptomyces antibioticus</i> OUCT16-23 using a genome-guided strategy coupled with bioassay. Their structures were elucidated based on the extensive MS and NMR spectroscopic analyses together with ECD calculations. In an antifungal assay, compounds <b>4</b>, <b>5</b>, and <b>7</b>-<b>10</b> showed different degrees of growth inhibition against <i>Candida albicans</i> with minimum inhibitory concentrations (MICs) of 1.56-12.5 μg/mL, by which the alkyl side-chain substitution affecting the activity was preliminarily studied. A biosynthetic pathway to <b>1</b>-<b>12</b> in <i>S. antibioticus</i> OUCT16-23 is also proposed.