Academic Journal

Assessing and harnessing updated polyketide synthase modules through combinatorial engineering

التفاصيل البيبلوغرافية
العنوان: Assessing and harnessing updated polyketide synthase modules through combinatorial engineering
المؤلفون: Katherine A. Ray, Joshua D. Lutgens, Ramesh Bista, Jie Zhang, Ronak R. Desai, Melissa Hirsch, Takeshi Miyazawa, Antonio Cordova, Adrian T. Keatinge-Clay
المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-12 (2024)
بيانات النشر: Nature Portfolio, 2024.
سنة النشر: 2024
المجموعة: LCC:Science
مصطلحات موضوعية: Science
الوصف: Abstract The modular nature of polyketide assembly lines and the significance of their products make them prime targets for combinatorial engineering. The recently updated module boundary has been successful for engineering short synthases, yet larger synthases constructed using the updated boundary have not been investigated. Here we describe our design and implementation of a BioBricks-like platform to rapidly construct 5 triketide, 25 tetraketide, and 125 pentaketide synthases to test every module combination of the pikromycin synthase. Anticipated products are detected from 60% of the triketide synthases, 32% of the tetraketide synthases, and 6.4% of the pentaketide synthases. We determine ketosynthase gatekeeping and module-skipping are the principal impediments to obtaining functional synthases. The platform is also employed to construct active hybrid synthases by incorporating modules from the erythromycin, spinosyn, and rapamycin assembly lines. The relaxed gatekeeping of a ketosynthase in the rapamycin synthase is especially encouraging in the quest to produce designer polyketides.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-024-50844-6
URL الوصول: https://doaj.org/article/9e99047681f6447ea911b207c472133d
رقم الانضمام: edsdoj.9e99047681f6447ea911b207c472133d
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20411723
DOI:10.1038/s41467-024-50844-6