Aparicio J F, Caffrey P, Gil J A, Zotchev S B
Inbiotec, Institute of Biotechnology of León, Av. Real 1, 24006, León, Spain.
Appl Microbiol Biotechnol. 2003 May;61(3):179-88. doi: 10.1007/s00253-002-1183-5. Epub 2002 Dec 18.
Over the past 15 years the biosynthetic gene clusters for numerous bioactive polyketides have been intensively studied and recently this work has been extended to the antifungal polyene macrolides. These compounds consist of large macrolactone rings that have a characteristic series of conjugated double bonds, as well as an exocyclic carboxyl group and an unusual mycosamine sugar. The biosynthetic gene clusters for nystatin, pimaricin, amphotericin and candicidin have been investigated in detail. These clusters contain the largest modular polyketide synthase genes reported to date. This body of work also provides insights into the enzymes catalysing the unusual post-polyketide modifications, and the genes regulating antibiotic biosynthesis. The sequences also provide clues about the evolutionary origins of polyene biosynthetic genes. Successful genetic manipulation of the producing organisms leading to production of polyene analogues indicates good prospects for generating improved antifungal compounds via genetic engineering.
在过去的15年里，众多生物活性聚酮化合物的生物合成基因簇得到了深入研究，最近这项工作已扩展到抗真菌多烯大环内酯类化合物。这些化合物由具有一系列共轭双键特征的大内酯环组成，还有一个环外羧基和一种不寻常的霉菌胺糖。制霉菌素、匹马霉素、两性霉素和杀假丝菌素的生物合成基因簇已得到详细研究。这些基因簇包含了迄今为止报道的最大的模块化聚酮合酶基因。这项工作还为催化聚酮化合物后异常修饰的酶以及调节抗生素生物合成的基因提供了见解。这些序列也为多烯生物合成基因的进化起源提供了线索。对产生这些化合物的生物体进行成功的基因操作，从而生产多烯类似物，这表明通过基因工程生产改良抗真菌化合物具有良好前景。
