(±)-FeionemycinA and Chromonemycins A–D,Rearranged Aromatic Polyketides Uncovered by Type II Polyketide GeneCluster Expression

Two novel spiro aromatic polyketides, (+)- and (−)-feionemycin A (<b>1</b>), along with four atypical angucyclinones named as chromonemycins A–D (<b>2</b>–<b>5</b>), 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 <b>1</b> features an unprecedented oxaspiro[5.4]undecane architecture, and compounds <b>2</b>–<b>5</b> 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. (+)-<b>1</b> showed cytotoxic activity against NCI-H446, with an IC₅₀ value of 2.26 μM.