Identification of functionally clustered nystatin-like biosynthetic genes in a rare actinomycetes, Pseudonocardia autotrophica
Identification of functionally clustered nystatin-like biosynthetic genes in a rare actinomycetes, Pseudonocardia autotrophica
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DOI：
10.1007/s10295-009-0629-5
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发表时间：
2009-11-01
影响因子：
3.4
通讯作者：
Kim, Eung-Soo
中科院分区：
文献类型：
--
作者：
Kim, Byung-Gyun;Lee, Mi-Jin;Kim, Eung-Soo
多烯抗生素，包括制霉菌素、匹马菌素、阿替霉素和杀念菌素，包括非常有价值的抗真菌聚酮化合物家族，并且它们通常由土壤放线菌产生。先前，使用多烯细胞色素P450羟化酶特异性基因组筛选策略，确定自养假诺卡氏菌KCTC 9441含有可能编码多烯生物合成的基因。在这里，从自养假单胞菌KCTC 9441基因组文库中分离的五个重叠粘粒中约125.7 kb连续DNA区域的序列信息揭示了总共23个开放阅读框，推测它们参与了暂时命名为NPP的制霉菌素样化合物的生物合成。六个多模块聚酮合酶（PKS）催化结构域的推断作用被发现是高度同源的那些先前确定制霉菌素生物合成基因。低的NPP生产力表明，功能性聚集的NPP生物合成途径基因在P.autotrophica中受到严格调控。破坏的NPP PKS基因完全废除了NPP生物合成和抗真菌活性对白色念珠菌，这表明多烯特异性基因组筛选可能构成一个有效的方法，用于分离潜在的有价值的先前确定的多烯基因和化合物从各种罕见的放线菌广泛分布在自然界中。
The polyene antibiotics, including nystatin, pimaricin, amphotericin, and candicidin, comprise a family of very valuable antifungal polyketide compounds, and they are typically produced by soil actinomycetes. Previously, using a polyene cytochrome P450 hydroxylase-specific genome screening strategy, Pseudonocardia autotrophica KCTC9441 was determined to contain genes potentially encoding polyene biosynthesis. Here, sequence information of an approximately 125.7-kb contiguous DNA region in five overlapping cosmids isolated from the P. autotrophica KCTC9441 genomic library revealed a total of 23 open reading frames, which are presumably involved in the biosynthesis of a nystatin-like compound tentatively named NPP. The deduced roles for six multi-modular polyketide synthase (PKS) catalytic domains were found to be highly homologous to those of previously identified nystatin biosynthetic genes. Low NPP productivity suggests that the functionally clustered NPP biosynthetic pathway genes are tightly regulated in P. autotrophica. Disruption of a NPP PKS gene completely abolished both NPP biosynthesis and antifungal activity against Candida albicans, suggesting that polyene-specific genome screening may constitute an efficient method for isolation of potentially valuable previously identified polyene genes and compounds from various rare actinomycetes widespread in nature.