TAXOL PRODUCTION AS INFLUENCED BY MICROBES

紫杉醇是目前最有前途的抗癌药物之一 正在调查中。临床试验已经证明了这种方法的有效性。 尤其是在乳腺癌和卵巢癌中 系统。限制紫杉醇更广泛使用的主要因素 就是它的可用性。在自然界中，它只存在于 红豆杉属植物，特别是在美国，野生物种 短叶红豆杉(太平洋红豆杉)。在这个项目中，我们试图 调查植物及其微生物中的这些因素 影响紫杉醇生产的环境。最初，我们将 使用涉及内部树皮碎片的体外系统来实现这一点 生物合成紫杉醇。该测试系统已经得到了验证。 我们现在寻求更全面地探索、隔离和识别那些 影响紫杉醇生产的内生真菌因素。 初步数据明确地表明， 真菌诱导子、赤霉酸和氯离子等化合物-- 氯化胆碱对紫杉醇生产的影响。另外，也可以想象 来自红豆杉的一种或多种内生真菌或细菌 能够产生紫杉醇或相关紫杉烷的。我们一直在 从无菌处理的样品中成功分离到至少50株真菌 里面的树皮。我们计划系统地对这些生物进行筛选 紫杉醇(紫杉烷)生产。现场研究，体外生产 树皮反应器中的紫杉醇，以及其他生物和化学因素 将研究控制紫杉醇的生产。

Taxol is one of the most promising anti-cancer drugs currently under investigation. Clinical trials have proven the usefulness of this compound especially in cancers of the breast and ovarian systems. The main factor limiting a more widespread use of taxol is its availability. In nature it is found exclusively in the plant genus Taxus and in particular in the U.S., the wild species Taxus brevifolia (Pacific yew). In this project we seek to investigate those factors in the plant and its microbial environment that influence taxol production. Initially, we will do this using an in vitro system involving inner bark pieces that biosynthesize taxol. This test system has already been proven. We now seek to more completely explore, isolate and identify those factors from endophytic fungi that affect taxol production. Preliminary data unequivocally have shown a positive influence of such compounds as fungal elicitors, gibberellic acid and chloro- choline chloride on taxol production. Also, it is also conceivable that one or more endophytic fungi or bacteria from Taxus are capable of producing taxol or a related taxane. We have been successful in isolating at least 50 fungi from aseptically treated inner bark. We plan to systematically screen these organisms for taxol (taxane) production. Field studies, in vitro production of taxol by a bark reactor, and other biological and chemical factors controlling taxol production will be studied.