Native and Engineered Clifednamide Biosynthesis in Multiple Streptomyces spp.,ACS Synthetic Biology

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Native and Engineered Clifednamide Biosynthesis in Multiple Streptomyces spp.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2017-12-20 00:00:00 , DOI: 10.1021/acssynbio.7b00349
Yunci Qi ₁ , Edward Ding ₁ , Joshua A. V. Blodgett ₁

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Polycyclic tetramate macrolactam (PTM) natural products are produced by actinomycetes and other bacteria. PTMs are often bioactive, and the simplicity of their biosynthetic clusters make them attractive for bioengineering. Clifednamide-type PTMs from Streptomyces sp. strain JV178 contain a distinctive ketone group, suggesting the existence of a novel PTM oxidizing enzyme. Here, we report the new cytochrome P450 enzyme (CftA) is required for clifednamide production. Genome mining was used to identify several new clifednamide producers, some having improved clifednamide yields. Using a parallel synthetic biology approach, CftA isozymes were used to engineer the ikarugamycin pathway of Streptomyces sp. strain NRRL F-2890 to yield clifednamides. Further, we observed that strong CftA expression leads to the production of a new PTM, clifednamide C. We demonstrate the utility of both genome mining and synthetic biology to rapidly increase clifednamide production.

中文翻译：

在多个链霉菌属物种中天然和工程设计的生物酰胺的生物合成。

多环四酸酯大内酰胺（PTM）天然产物是由放线菌和其他细菌生产的。PTM通常具有生物活性，其生物合成簇的简单性使其对生物工程具有吸引力。来自链霉菌属的Clifednamide型PTM 。JV178菌株含有一个独特的酮基，表明存在一种新型的PTM氧化酶。在这里，我们报告了新的细胞色素P450酶（CftA）是生产clifednamide所必需的。基因组采矿被用来确定几种新的生物酰胺的生产者，其中一些具有提高的生物酰胺产量。使用平行合成生物学方法，CftA同工酶用于工程化链霉菌的ikarugamycin途径sp。菌株NRRL F-2890，以产生环丙酰胺。此外，我们观察到强CftA表达可导致产生新的PTM克雷尼酰胺C。我们证明了基因组挖掘和合成生物学在快速增加克雷尼酰胺产量中的实用性。

更新日期：2017-12-20

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