Hye-Dong Yoo

Absolute configuration of curacin A, a novel antimitotic agent from the tropical marine cyanobacterium Lyngbya majuscula

Curacin A is a structurally novel antimitotic agent isolated from the Caribbean cyanobacterium Lyngbya majuscula. Its planar structure has been previously determined from a spectroscopic investigation. Here, we define the complete relative and absolute configuration of curacin A by comparison of products obtained from chemical degradation of the natural product with the same substances prepared by synthesis. Curacin A is shown to have 2R, 13R, 19R, 21S absolute configuration.

Production of hydroxy fatty acids by cell suspension cultures of the marine brown alga Laminaria saccharina

Abstract Photolithotrophic cell suspension cultures established from the microscopic gametophytic life phase of Laminaria saccharina produced three hydroxy fatty acids deriving from an ω-6 lipoxygenase (LOX) oxidation: 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), 13-hydroxy-6,9,11,15-octadecatetraenoic acid (13-HODTA), and 13-hydroxy-9,11-octadecadienoic acid (13-HODE). The yields of 15-HETE, 13-HODTA, and 13-HODE ranged from 100 to 1000 μg product g−1 dry biomass. In the attempt to stimulate ω-6 LOX metabolism in vitro, three C18 polyunsaturated fatty acids, including linoleic, α-linolenic, and γ-linolenic acid were added separately to the culture medium after 20 days of cultivation and then allowed to incubate with the culture for 10 days. Linoleic and γ-linolenic acid increased the yield of all three hydroxy fatty acids from 2 to 4 times over controls, with 15-HETE showing the most significant increase. In contrast, α-linolenic acid was toxic to the culture at 200 mg 1−1.

Pilot scale culture of the marine cyanobacterium Lyngbya majuscula for its pharmaceutically-useful natural metabolite curacin A

A Caribbean collection of Lyngbya majuscula which produces the promising antimitotic agent, curacin A, was recollected in 1993 from Curaçao and adapted to laboratory culture. A variety of culture vessel configurations and conditions were examined for their effect on growth and production of curacin A. Using these partially optimized conditions, 29 strains of curacin A producing L. majuscula were evaluated for their production levels of curacin A employing an internal standard GC-MS analytical method. Five strains were more carefully characterized for their growth and curacin A production, and led to our selection of one reliable strain, ’19L‘, for further studies. Growth and curacin A production curves were established for this strain over a 30 day growth period. This directed a scale-up culture of 640 liters of L. majuscula strain 19L in four batches of 160 L each. All four batches grew well and produced significant quantities of curacin A. In tota1, 215.5 g wet weight of L. majuscula tissue were produced which gave an isolated yield of 132.5 mg of curacin A.

Bioreactor seaweed cell culture for production of bioactive oxylipins

Liquid cell suspension cultures derived from marine plants have the potential to biosynthesize novel biomedicinal compounds in a controlled environment. Of particular interest are the eicosanoids and related oxylipins emanating from the 15-lipoxygenase manifold of the arachidonic acid cascade, which is active in the brown algaLaminaria saccharina. Filamentous cell clumps ofL. saccharina isolated from female gametophytes were cultured in an illuminated bubble-column bioreactor in GP2 artificial seawater nutrient medium at 13 °C and air flow rate of 0.35 L air min−1 L−1 culture (vvm). Growth kinetics and biomass productivity data were obtained as a function of incident light intensity (2.4 to 98μmol photon m−2 s−1) and initial cell density (27 to 149 mg DCW L−1). Maximum cell densities exceeded 1200 mg DCW L−1 after a 20 day cultivation time at optimal conditions of 98μmol photon m−2 s−1 and 118 mg DCW L−1 initial cell density. Qualitative analysis of chloroform/methanol extracts of the cell culture biomass by GC-MS confirmed the presence of the hydroxy fatty acids 13-HODTA and 13-HOTE, the likely products of 15-lipoxygenase catalyzed oxidation of linoleic or linolenic acids.

Discovery of Novel Cannabinoid Receptor Ligands from Diverse Marine Organisms

Arachidonic acid ethanolamide (anandamide), a simple nitrogen-containing lipid, has recently been described as an endogenous ligand to the mammalian CNS cannabinoid receptor (CB1)1. Since its initial characterization, there has been tremendous interest in exploring a diversity of related structures for activity at this receptor from the viewpoint of defining structure-activity relationships at this receptor, discovering pharmacologically useful agonists and antagonists, and defining the role of anandamide metabolism in the modulation of CB1 activation2.

Isoflavones from Psorothamnus arborescens via high-throughput natural product chemistry methods

One new isoflavone, arborestin (2), together with the known fremontin (1), were obtained from Psorothamnus arborescens via high-throughput natural product chemistry methods. The isoflavones were isolated and the structure elucidation was performed using a capillary scale NMR probe and HR-/LR-ESIMS data.