10.1021/jo0267596.s001 Hideaki Oikawa Hideaki Oikawa Biosynthesis of Structurally Unique Fungal Metabolite GKK1032A<sub>2</sub>:  Indication of Novel Carbocyclic Formation Mechanism in Polyketide Biosynthesis American Chemical Society 2003 polyketide chain nonribosomal peptide synthetase Novel Carbocyclic Formation Mechanism oxidation level GKK 1032. antitumor agent GKK 1032A 2 biosynthesi macroether nonaketide chain novel cyclization mechanisms starter unit 13 C tyrosine hydroxy group Penicillium sp methyl groups polyketide synthase Polyketide Biosynthesis 2 H tricarbocyclic system formation 2003-03-28 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Biosynthesis_of_Structurally_Unique_Fungal_Metabolite_GKK1032A_sub_2_sub_Indication_of_Novel_Carbocyclic_Formation_Mechanism_in_Polyketide_Biosynthesis/3697590 The biosynthesis of the antitumor agent GKK1032A<sub>2</sub> (<b>1) </b>has been investigated by administration of isotopically labeled (<sup>13</sup>C and <sup>2</sup>H) precursors to <i>Penicillium</i> sp. GKK1032. These studies showed that the backbone of <b>1</b> is constructed from l-tyrosine and a nonaketide chain flanked with five methyl groups probably by a polyketide synthase and a nonribosomal peptide synthetase hybrid. On the basis of the oxidation level of the starter unit and unusual 13-membered macroether formation between the tyrosine hydroxy group and the polyketide chain, novel cyclization mechanisms on the formation of a tricarbocyclic system and a macroether have been proposed. Involvement of a similar type of cyclization in the biosynthesis of structurally related metabolites is discussed.