Biosynthesis of Secondary Metabolites from Blue-Green Algae

本研究将探讨蓝绿藻次生代谢物生物合成的几个特定领域。第一批被研究的化合物包括：来自水藻的强效抗胆碱酯酶anatoxin-a(s)，来自铜绿微胞菌的肝毒性环肽微囊素- lr和来自刺毛结核菌的结核素，来自agardhii的神经毒性生物碱anatoxin-a和homanatoxin -a，以及炎性因子lynbyatoxin A和debromoaplysiatoxin来自lynbya majuscula。还将对蓝藻中新毒素的分离、结构测定和生物合成进行研究。第二个主要领域将集中于继续研究来自于海龙的杀菌剂吲哚生物碱hapalinole a和毒毒素，mirabilene a异腈，mirabimide E和tantazole B的生物合成，这是来自于海龙的四类结构独特和多样化的天然产物的代表。第三个领域的研究将涉及从地衣柱孢中生物合成圆柱环烷a，第一种ım，n！自然界中发现的副环环菌素，以及一种在地衣原体中刺激孢子形成的细胞外物质。最后，研究将从蓝绿藻中分离、结构测定和生物合成其他不寻常的天然产物，例如从海洋蓝藻长聚藻中提取的抗病毒化合物聚藻素；以及从属于刺藻门的蓝藻中提取的新生物碱。有了这笔奖金，化学分部的合成有机项目将支持夏威夷大学马诺阿分校化学系理查德·e·摩尔博士的研究。该研究的主要目标是了解蓝绿藻中次生代谢物的生物合成，特别是淡水、微咸水和海洋蓝藻，它们产生的毒素与野生动物、家畜和人类中毒有关。

This research will address several specific areas of secondary metabolite biosynthesis in blue-green algae. The first group of compounds to be investigated includes the potent anticholinesterase anatoxin-a(s) from Anabaena flos-aquae, the hepatotoxic cyclic peptides microcystin-LR from Microcytis aeruginosa and nodularin from Nodularia spumigena, the neurotoxic alkaloids anatoxin-a and homoanatoxin-a from Oscillatoria agardhii, and the inflammatory agents lyngbyatoxin A and debromoaplysiatoxin from Lyngbya majuscula. Studies also will be carried out on the isolation, structure determination and biosynthesis of new toxins from cyanophytes. The second major area will focus on a continuation of studies on the biosynthesis of hapalindole A, a fungicidal indole alkaloid from Hapalosiphon fontinalis, and tolytoxin, mirabilene A isonitrile, mirabimide E, and tantazole B, representatives of four classes of structurally unique and diverse natural products from Scytonema mirabile. Studies in a third area will involve the biosynthesis of cylindrocyclophane A from Cylindrospermum licheniforme, the first ım,n!paracyclophane to be found in Nature, and an extracellular substance which stimulates sporulation in C. licheniforme. Finally studies will be carried out on the isolation, structure determination, and biosynthesis of other unusual natural products from blue-green algae, e.g. synechocin, an antiviral compound from the marine cyanophyte Synechococcus elongatus, and new alkaloids from cyanophytes belonging to the Stigonematales. %%% With this award the Synthetic Organic Program of the Chemistry Division will support the research of Dr. Richard E. Moore of the Department of Chemistry at the University of Hawaii, Manoa. The major goal of the research is to understand the biosynthesis of secondary metabolites in blue-green algae, especially freshwater, brackish-water, and marine cyanophytes which produce toxins implicated in wildlife, domestic animal, and human poisonings.