(±)-Feionemycin A and Chromonemycins A-D, Rearranged Aromatic Polyketides Uncovered by Type II Polyketide Gene
Xiaofei Huang1, Xiao Xu1, Luning Zhou1
1Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.
Abstract:
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.
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