<jats:title>Abstract</jats:title><jats:p>Xanthocidin and six new derivatives were isolated from the endophytic <jats:italic>Streptomyces</jats:italic> sp. AcE210. Their planar structures were elucidated by 1D and 2D NMR spectroscopy as well as by HRMS. The absolute configuration of one compound was determined by using vibrational circular dichroism spectroscopy (VCD). The structural similarities of xanthocidin and some of the isolated xanthocidin congeners to the methylenomycins A, B, and C suggested that the biosynthesis of these compounds might follow a similar route. Feeding studies with isotopically labelled [<jats:sup>13</jats:sup>C<jats:sub>5</jats:sub>]‐<jats:sc>l</jats:sc>‐valine showed that instead of utilizing acetyl‐CoA as starter unit, which has been proposed for the methylenomycin biosynthesis, <jats:italic>Streptomyces</jats:italic> sp. AcE210 employs an isobutyryl‐CoA starter unit, resulting in a branched side chain in xanthocidin. Further evidence for a comparable biosynthesis was given by the analysis of the genome sequence of <jats:italic>Streptomyces</jats:italic> sp. AcE210 that revealed a cluster of homologues to the <jats:italic>mmy</jats:italic> genes involved in methylenomycin biosynthesis.