title: Structural modification of herboxidiene by substrate-flexible cytochrome P450 and glycosyltransferase.
abstract: Herboxidiene is a natural product produced by Streptomyces chromofuscus exhibiting herbicidal activity as well as antitumor properties. Using different substrate-flexible cytochrome P450s and glycosyltransferase, different novel derivatives of herboxidiene were generated with structural modifications by hydroxylation or epoxidation or conjugation with a glucose moiety. Moreover, two isomers of herboxidiene containing extra tetrahydrofuran or tetrahydropyran moiety in addition to the existing tetrahydropyran moiety were characterized. The hydroxylated products for both of these compounds were also isolated and characterized from S. chromofuscus PikC harboring pikC from the pikromycin gene cluster of Streptomyces venezuelae and S. chromofuscus EryF harboring eryF from the erythromycin gene cluster of Saccharopolyspora erythraea. The compounds generated were characterized by high-resolution quadrupole-time-of-flight electrospray ionization mass spectrometry (HR-QTOF-ESI/MS) and (1)H- and (13)C-nuclear magnetic resonance (NMR) analyses. The evaluation of antibacterial activity against three Gram-positive bacteria, Micrococcus luteus, Bacillus subtilis, and Staphylococcus aureus, indicated that modification resulted in a transition from anticancer to antibacterial potency.
authors: Institute of Biomolecule Reconstruction (iBR), Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-Ro221, Tangjeong-myeon, Asan, Chungnam, 333-708, Republic of Korea.
authors: Amit Kumar
authors: AK
authors: Jha
authors: Dipesh
authors: D
authors: Dhakal
authors: Pham Thi Thuy
authors: PT
authors: Van
authors: Anaya Raj
authors: AR
authors: Pokhrel
authors: Tokutaro
authors: T
authors: Yamaguchi
authors: Hye Jin
authors: HJ
authors: Jung
authors: Yeo Joon
authors: YJ
authors: Yoon
authors: Jae Kyung
authors: JK
authors: Sohng
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001407:Bacillus / Q000187:drug effects / Q000254:growth & development; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism*; D060847:Metabolic Engineering; D016982:Micrococcus luteus / Q000187:drug effects / Q000254:growth & development; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016930:Saccharopolyspora / Q000201:enzymology / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D005233:Fatty Alcohols; D011714:Pyrans; D011994:Recombinant Proteins; C076087:herboxidiene; D003577:Cytochrome P-450 Enzyme System; D016695:Glycosyltransferases