Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics.
Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics.
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DOI：
10.1590/s1517-83822013000400002
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
de Macedo Lemos EG
中科院分区：
文献类型：
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作者：
Gomes ES;Schuch V;de Macedo Lemos EG
微生物产生的次级代谢产物的发现（例如，青霉素的发明（1928年）及其工业应用的开始（1940年）为治疗传染病和肿瘤的主要药物来源打开了新的大门。事实上，在发现第一种抗生素化合物大约80年后，尽管有关于“下金蛋的鹅”失败的所有警告，但这种财富的潜力仍然是不可阻挡的：只需将焦点从“微米”调整到“纳米”，这意味着将外观从微生物改变为纳克DNA。然后，由基因工程与宏基因组策略相结合驱动的新药研究向我们展示了一种绕过限于分离和培养的方法所施加的障碍的方法。然而，我们远未解决提供有效对抗多重或泛耐药病原体可塑性的新分子的问题。尽管基因工程的第一次进展可以追溯到1990年，但仍然缺乏高通量方法来加速新基因的筛选和通过重组途径设计新分子。此外，有必要增加异源宿主的种类，并在整个药物发现管道中进行改进。在众多的研究集中在这个问题上，那些对聚酮抗生素脱颖而出的大型技术科学的努力，建立了新的解决方案，转移/工程的主要代谢途径使用转座子和其他附加体，克服了一个主要的方法学的限制异源表达的主要途径。三维酶结构的计算机预测分析和测序技术的进步扩大了对微生物代谢潜力的利用。
The discovery of secondary metabolites produced by microorganisms (e.g., penicillin in 1928) and the beginning of their industrial application (1940) opened new doors to what has been the main medication source for the treatment of infectious diseases and tumors. In fact, approximately 80 years after the discovery of the first antibiotic compound, and despite all of the warnings about the failure of the “goose that laid the golden egg,” the potential of this wealth is still inexorable: simply adjust the focus from “micro” to “nano”, that means changing the look from microorganisms to nanograms of DNA. Then, the search for new drugs, driven by genetic engineering combined with metagenomic strategies, shows us a way to bypass the barriers imposed by methodologies limited to isolation and culturing. However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens. Although the first advances in genetic engineering date back to 1990, there is still a lack of high-throughput methods to speed up the screening of new genes and design new molecules by recombination of pathways. In addition, it is necessary an increase in the variety of heterologous hosts and improvements throughout the full drug discovery pipeline. Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways. In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms.