(±)-Feionemycin A and Chromonemycins A–D, Rearranged Aromatic Polyketides Uncovered by Type II Polyketide Gene Cluster Expression

Two novel spiro aromatic polyketides, (+)- and (−)-feionemycin A (1), along with four atypical angucyclinones named as chromonemycins A–D (2–5), were discovered through heterologous expression of a type II polyketide gene cluster, within which one previously characterized flavoprotein monooxygenase was deactivated. Among those structures, compound 1 features an unprecedented oxaspiro[5.4]undecane architecture, and compounds 2–5 represent novel atypical angucyclinone variants derived from unusual cyclization of the polyketide chains. The structures and absolute configurations were elucidated by NMR, MS, single-crystal X-ray diffraction, theoretical NMR calculations, DP4+ probability analysis, and ECD analyses. (+)-1 showed cytotoxic activity against NCI-H446, with an IC50 value of 2.26 μM.