Department of Information and Communications Engineering, KAIST, Daejeon, 305-701, South Korea.
BMC Microbiol. 2012 Aug 8;12:169. doi: 10.1186/1471-2180-12-169.
Bacterial aromatic polyketides are a pharmacologically important group of natural products synthesized by type II polyketide synthases (type II PKSs) in actinobacteria. Isolation of novel aromatic polyketides from microbial sources is currently impeded because of the lack of knowledge about prolific taxa for polyketide synthesis and the difficulties in finding and optimizing target microorganisms. Comprehensive analysis of type II PKSs and the prediction of possible polyketide chemotypes in various actinobacterial genomes will thus enable the discovery or synthesis of novel polyketides in the most plausible microorganisms.
We performed a comprehensive computational analysis of type II PKSs and their gene clusters in actinobacterial genomes. By identifying type II PKS subclasses from the sequence analysis of 280 known type II PKSs, we developed highly accurate domain classifiers for these subclasses and derived prediction rules for aromatic polyketide chemotypes generated by different combinations of type II PKS domains. Using 319 available actinobacterial genomes, we predicted 231 type II PKSs from 40 PKS gene clusters in 25 actinobacterial genomes, and polyketide chemotypes corresponding to 22 novel PKS gene clusters in 16 genomes. These results showed that the microorganisms capable of producing aromatic polyketides are specifically distributed within a certain suborder of Actinomycetales such as Catenulisporineae, Frankineae, Micrococcineae, Micromonosporineae, Pseudonocardineae, Streptomycineae, and Streptosporangineae.
We could identify the novel candidates of type II PKS gene clusters and their polyketide chemotypes in actinobacterial genomes by comprehensive analysis of type II PKSs and prediction of aromatic polyketides. The genome analysis results indicated that the specific suborders in actinomycetes could be used as prolific taxa for polyketide synthesis. The chemotype-prediction rules with the suggested type II PKS modules derived using this resource can be used further for microbial engineering to produce various aromatic polyketides. All these resources, together with the results of the analysis, are organized into an easy-to-use database PKMiner, which is accessible at the following URL: http://pks.kaist.ac.kr/pkminer. We believe that this web-based tool would be useful for research in the discovery of novel bacterial aromatic polyketides.
细菌芳香族聚酮化合物是一类具有重要药理学意义的天然产物，由放线菌中的 II 型聚酮合酶（type II PKSs）合成。由于缺乏对聚酮合成高产种的了解，以及寻找和优化目标微生物的困难，从微生物来源中分离新型芳香族聚酮化合物目前受到阻碍。因此，对 II 型 PKS 进行全面分析，并预测各种放线菌基因组中可能的聚酮化学型，将使最有可能产生新型聚酮的微生物得到发现或合成。
我们对放线菌基因组中的 II 型 PKS 及其基因簇进行了全面的计算分析。通过对 280 种已知 II 型 PKS 的序列分析，确定了 II 型 PKS 的亚类，我们为这些亚类开发了高度准确的结构域分类器，并得出了不同 II 型 PKS 结构域组合生成的芳香族聚酮化学型的预测规则。利用 319 个可用的放线菌基因组，我们从 25 个放线菌基因组中的 40 个 PKS 基因簇中预测了 231 个 II 型 PKS，并预测了 16 个基因组中 22 个新型 PKS 基因簇对应的聚酮化学型。结果表明，能够产生芳香族聚酮的微生物专门分布在放线菌目中的特定亚目，如链霉菌亚目、弗兰克氏菌亚目、微球菌亚目、小单孢菌亚目、诺卡氏菌亚目、链霉菌亚目和链孢囊菌亚目。
通过对 II 型 PKS 的全面分析和芳香族聚酮的预测，我们可以在放线菌基因组中鉴定出新型 II 型 PKS 基因簇及其聚酮化学型的候选者。基因组分析结果表明，放线菌中的特定亚目可以作为聚酮合成的高产种。利用该资源推导的具有建议的 II 型 PKS 模块的化学型预测规则可进一步用于微生物工程，以生产各种芳香族聚酮。所有这些资源以及分析结果都组织到一个易于使用的数据库 PKMiner 中，可通过以下网址访问：http://pks.kaist.ac.kr/pkminer。我们相信，这个基于网络的工具对于发现新型细菌芳香族聚酮的研究将非常有用。
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