Recoding of synonymous genes to expand evolutionary landscapes requires control of secondary structure affecting translation

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Escudero García-Calderón, José Antonio and Nivina, Aleksandra and Cambray, Guillaume and López Igual, Rocío and Loot, Céline and Mazel, Didier (2017) Recoding of synonymous genes to expand evolutionary landscapes requires control of secondary structure affecting translation. Biotechnology and Bioengineering., 115 (1). pp. 184-191. ISSN 1097-0290

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Official URL: https://doi.org/10.1002/bit.26450



Abstract

Synthetic DNA design needs to harness the many information layers embedded in a DNA string. We previously developed the Evolutionary Landscape Painter (ELP), an algorithm that exploits the degeneracy of the code to increase protein evolvability. Here, we have used ELP to recode the integron integrase gene (intI1) in two alternative alleles. Although synonymous, both alleles yielded less IntI1 protein and were less active in recombination assays than intI1. We spliced the three alleles and mapped the activity decrease to the beginning of alternative sequences. Mfold predicted the presence of more stable secondary structures in the alternative genes. Using synonymous mutations, we decreased their stability and recovered full activity. Following a design-build-test approach, we have now updated ELP to consider such structures and provide streamlined alternative sequences. Our results support the possibility of modulating gene activity through the ad hoc design of 5′ secondary structures in synthetic genes.


Item Type:Article
Uncontrolled Keywords:DNA design, integrons, mRNA secondary structure, optimized gene, synonymous genes, synthetic biology
Subjects:Medical sciences > Veterinary > Microbiology
Medical sciences > Biology > Molecular biology
Medical sciences > Biology > Biotechnology
Medical sciences > Biology > Evolution
Medical sciences > Biology > Microbiology
ID Code:70812
Deposited On:28 Feb 2022 12:53
Last Modified:04 Apr 2022 15:15

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