کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8406354 | 1544938 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Integrated constraints based analysis of an engineered violacein pathway in Escherichia coli
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
ریاضیات
مدلسازی و شبیه سازی
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چکیده انگلیسی
Strategies towards optimal violacein biosynthesis, a potential drug molecule, need systems level coordination of enzymatic activities of individual genes in a multigene operon vioABCDE. Constraints-based flux balance analysis of an extended iAF1260 model (iAF1260vio) with a reconstructed violacein module predicted growth and violacein yields in Escherichia coli accurately. Shadow price (SP) analysis identified tryptophan metabolism and NADPH as limiting. Increased tryptophan levels in Îpgi & ÎpheA were validated using in silico gene deletion analysis. Phenotypic phase plane (PhPP) analysis highlighted sensitivity between tryptophan and NADPH for violacein synthesis at molar growth yields. A synthetic VioABCDE operon (SYNO) sequence was designed to maximize Codon Adaptive Index (CAI: 0.9) and tune translation initiation rates (TIR: 2-50 fold higher) in E. coli. All pSYN E. coli transformants produced higher violacein, with a maximum six-fold increase in yields. The rational design E. coli: ÎpheA SYN: gave the highest violacein titers (33.8â¯mg/l). Such integrated approaches targeting multiple molecular hierarchies in the cell can be extended further to increase violacein yields.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biosystems - Volume 171, September 2018, Pages 10-19
Journal: Biosystems - Volume 171, September 2018, Pages 10-19
نویسندگان
Selva Rupa Christinal Immanuel, Deepanwita Banerjee, Mayooreshwar P. Rajankar, Anu Raghunathan,