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

Biotechnology and bioengineering publish this investigation article

January 1st, 2018

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. This article is protected by copyright. All rights reserved




Escudero JA., Nivina A., Cambray G., Lopez-Igual R., Loot C. and Mazel D.




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

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



Participants:

Institut PasteurDepartment of Genomes and Genetics. Institut Pasteur.

Centre National de la Recherche ScientifiqueCentre National de la Recherche Scientifique (CNRS).

Universidad ComplutenseDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Universidad ComplutenseServicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

Université Sorbonne Paris DescartesUniversité Sorbonne Paris Descartes.

Institut National de la Recherche AgronomiqueInstitut National de la Recherche Agronomique (INRA).







FACTOR YEAR Q
4.260 2018

NLMID: 7502021

PMID: 28898391

ISSN: 0006-3592



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


JOURNAL: Biotechnol Bioeng


NUMERACIÓN: 115(1):184-191


AÑO: 2018


PUBLISHER: Periodicals


AUTHORS: Escudero JA., Nivina A., Cambray G., Lopez-Igual R., Loot C. and Mazel D.


VISAVET PARTICIPANTS


José Antonio Escudero García-Calderón

DOI: https://doi.org/10.1002/bit.26450


CITE THIS PUBLICATION:

Escudero JA., Nivina A., Cambray G., Lopez-Igual R., Loot C. and Mazel D. Recoding of synonymous genes to expand evolutionary landscapes requires control of secondary structure affecting translation. Biotechnology and bioengineering. 115(1):184-191. 2018. (A). ISSN: 0006-3592. DOI: 10.1002/bit.26450


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