Multi-oxygenase complexes of the gilvocarcin and jadomycin biosyntheses.

  title={Multi-oxygenase complexes of the gilvocarcin and jadomycin biosyntheses.},
  author={M. Kharel and Lili Zhu and Tao Liu and J. Rohr},
  journal={Journal of the American Chemical Society},
  volume={129 13},
The biosyntheses of the gilvocarcins (e.g., gilvocarcin V, 6, scheme 1), and jadomycins (e.g., jadomycin B, 4) are both dominated by oxidative rearrangement cascades that lead from simple polyketide-derived angucyclinones to the unique tetracyclic benzo[d]naphtho[1,2-b]pyran-6-one and pentacyclic benz[b]oxazolophenanthridine backbones, respectively, which are typical and essential for these anticancer antibiotics. Previous work showed that UWM6 (1a) and prejadomycin (= 2,3-dehydro-UWM6, 2a) or… Expand
Enzymatic total synthesis of defucogilvocarcin M and its implications for gilvocarcin biosynthesis.
A complete, one-pot, enzymatic total synthesis of defucogilvocarcin M(1), a model compound that contains the unique chromophore common to all members of the gil Vocarcin group of natural products is reported. Expand
OF DISSERTATION INVESTIGATING KEY POST-PKS ENZYMES FROM GILVOCARCIN BIOSYNTHETIC PATHWAY Gilvocarcin V (GV) belongs to the angucycline class of antibiotics that possesses remarkable anticancer andExpand
Native roles of Baeyer-Villiger monooxygenases in the microbial metabolism of natural compounds.
The inherent roles of type I, type II and type O BVMOs in the metabolism of microorganisms are discussed, which often have attractive biological properties and can have clinical applications. Expand
Delineation of gilvocarcin, jadomycin, and landomycin pathways through combinatorial biosynthetic enzymology.
Investigations of the complex biosyntheses of the angucycline group anticancer drugs landomycin, jadomycin and gilvocarcin revealed that in vivo and in silico studies were insufficient to delineate the true biosynthetic sequence of events. Expand
Plasticity in gilvocarcin-type C-glycoside pathways: discovery and antitumoral evaluation of polycarcin V from Streptomyces polyformus.
Cytotoxicity profiling of polycarcin V in a panel of 37 tumor cell lines indicated significant antitumoral activity with a pronounced selectivity for non-small-cell lung cancer, breast cancer and melanoma cells. Expand
Elucidation of post-PKS tailoring steps involved in landomycin biosynthesis.
The results revealed that LanM2 acts as a dehydratase and is responsible for concomitant release of the last PKS-tethered intermediate to yield prejadomycin (10), which was confirmed to be a general pathway intermediate of the biosynthesis. Expand
Synergistic Actions of a Monooxygenase and Cyclases in Aromatic Polyketide Biosynthesis
The recent sequencing of the benastatin and fredericamycin gene clusters, in conjunction with genetic and biochemical experiments, have provided insights into the biosynthesis of this class of polyketides, however, the regioselective cyclization steps that yield the pentangular core have remained uncharacterized. Expand
Crystal structure of Baeyer-Villiger monooxygenase MtmOIV, the key enzyme of the mithramycin biosynthetic pathway .
The three-dimensional structure of MtmOIV, a 56 kDa homodimeric FAD- and NADPH-dependent monooxygenase, which catalyzes the key frame-modifying step of the mithramycin biosynthetic pathway and currently the only BVMO proven to react with its natural substrate via a Baeyer-Villiger reaction, is presented. Expand
A biosynthetic pathway for BE-7585A, a 2-thiosugar-containing angucycline-type natural product.
The results indicated an unusual manner of angular tetracyclic ring construction, perhaps via a Baeyer-Villiger type rearrangement, which set the stage for future biochemical studies of 2-thiosugar biosynthesis and BE-7585A assembly. Expand
The functional differentiation of the post-PKS tailoring oxygenases contributed to the chemical diversities of atypical angucyclines
  • K. Fan, Q. Zhang
  • Chemistry, Medicine
  • Synthetic and systems biotechnology
  • 2018
The results suggested that the functional differentiation of these oxygenases could apparently enrich the sources of aromatic polyketides with greater structure diversities. Expand