A labile point in mutant amphotericin polyketide synthases
A labile point in mutant amphotericin polyketide synthases
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DOI：
10.1007/s10529-011-0538-3
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发表时间：
2011-01
影响因子：
2.7
通讯作者：
Naseem Khan;B. Rawlings;P. Caffrey
中科院分区：
文献类型：
--
作者：
Naseem Khan;B. Rawlings;P. Caffrey
结瘤链霉菌产生抗真菌的多烯阿替霉素B。许多修饰的阿氏菌素聚酮合酶已经产生了新的类似物。然而，模块10中酮还原酶的先前失活导致截短聚酮化合物的生物合成。在这里，我们表明，该域的下游模块保持完整。因此，酮还原酶-10活性的丧失足以引起早期链终止。这种修饰在聚酮化合物生物合成途径的循环11中产生不稳定点。不可延伸的中间体被释放以多烯基吡喃酮的形式积累。
Streptomyces nodosusproduces the antifungal polyene amphotericin B. Numerous modifications of the amphotericin polyketide synthase have yielded new analogues. However, previous inactivation of the ketoreductase in module 10 resulted in biosynthesis of truncated polyketides. Here we show that modules downstream of this domain remain intact. Therefore, loss of ketoreductase-10 activity is sufficient to cause early chain termination. This modification creates a labile point in cycle 11 of the polyketide biosynthetic pathway. Non-extendable intermediates are released to accumulate as polyenyl-pyrones.