Enhancement of nystatin production by redirecting precursor fluxes after disruption of the tetramycin gene from Streptomyces ahygroscopicus
Enhancement of nystatin production by redirecting precursor fluxes after disruption of the tetramycin gene from Streptomyces ahygroscopicus
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DOI：
10.1016/j.micres.2013.09.017
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发表时间：
2014-01-01
影响因子：
6.7
通讯作者：
Xia, Huanzhang
中科院分区：
文献类型：
--
作者：
Ren, Jun;Cui, Yuqiong;Xia, Huanzhang
从无吸湿链霉菌（Streptomyces ahygroscopicus）中分离到完整且独立的含有不同长度的I型聚酮合成酶（PKS）基因簇，该菌株大量产生四霉素（一种四烯），少量产生制霉菌素A1（一种七烯）。土霉素与海马霉素相似，制霉菌素A1与两性霉素相似。这些多烯大环内酯类抗生素均具有相同的由pks由辅酶A前体生物合成的大内酯环，但大内酯环和侧基的原子数不同。由于红霉素和制霉菌素在产糖生物体内共享有限的辅酶A前体，阻断红霉素途径中前体的消耗可能会增加辅酶A库。因此，我们通过基因操作来提高制霉菌素的产量。I型PKS ttmS1基因突变体消除了土霉素的产生，并对制霉菌素A1的产生产生了有益的影响。对于突变体，制霉菌素A1的产量比野生型增加了10倍。因此，四霉素途径的缺失重定向了前体代谢通量，并提供了一种简单的遗传方法来操纵生物体并增加精确目标的生产水平。(C) 2013爱思唯尔有限公司版权所有。
Complete and independent tetramycin and nystatin gene clusters containing varying lengths of type I polyketide synthase (PKS) genes were isolated from Streptomyces ahygroscopicus, a producer of tetramycin (a tetraene) in large amounts and nystatin A1 (a heptaene) in small amounts. Tetramycin was similar to pimaricin, and nystatin A1 was similar to amphotericin. All these polyene macrolide antibiotics possessed the same macrolactone ring biosynthesized from coenzyme A precursors by PKSs but had different number of atoms in the macrolactone ring and side groups. Because tetramycin and nystatin shared limited coenzyme A precursors in the sartie producer organism, blocking the consumption of precursors in tetramycin pathway may increase the coenzyme A pool. Thus,we genetically manipulated the tetramycin PKS to enhance nystatin production. The type I PKS ttmS1 gene mutant abolished production of tetramycin and had a beneficial effect on the production of nystatin A1. For the mutant, the yield of nystatin A1 was increased by 10-fold compared to that of the wild-type. Thus, deletion of the tetramycin pathway redirected precursor metabolic fluxes and provided an easy genetic approach to manipulate organisms and to increase production levels of a precise target. (C) 2013 Elsevier GmbH. All rights reserved.