کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
6452706 1418338 2017 13 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Multiplexed site-specific genome engineering for overproducing bioactive secondary metabolites in actinomycetes
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موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
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Multiplexed site-specific genome engineering for overproducing bioactive secondary metabolites in actinomycetes
چکیده انگلیسی


- A general approach for the stable amplification of secondary metabolite biosynthetic gene clusters in actinomycetes.
- A panel of powerful Streptomyces coelicolor heterologous hosts for genome mining of natural products.
- A novel DNA editing method for rapidly refactoring gene clusters, including deletion and replacement.

Actinomycetes produce a large variety of pharmaceutically active compounds, yet production titers often require to be improved for discovery, development and large-scale manufacturing. Here, we describe a new technique, multiplexed site-specific genome engineering (MSGE) via the 'one integrase-multiple attB sites' concept, for the stable integration of secondary metabolite biosynthetic gene clusters (BGCs). Using MSGE, we achieved five-copy chromosomal integration of the pristinamycin II (PII) BGC in Streptomyces pristinaespiralis, resulting in the highest reported PII titers in flask and batch fermentations (2.2 and 2 g/L, respectively). Furthermore, MSGE was successfully extended to develop a panel of powerful Streptomyces coelicolor heterologous hosts, in which up to four copies of the BGCs for chloramphenicol or anti-tumour compound YM-216391 were efficiently integrated in a single step, leading to significantly elevated productivity (2-23 times). Our multiplexed approach holds great potential for robust genome engineering of industrial actinomycetes and novel drug discovery by genome mining.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Metabolic Engineering - Volume 40, March 2017, Pages 80-92
نویسندگان
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