Evidence map›Paper›PMID 39833175›Full record

ArticleNature communications2025

Construction and iterative redesign of synXVI a 903 kb synthetic Saccharomyces cerevisiae chromosome.

Hugh D Goold, Heinrich Kroukamp, Paige E Erpf, Yu Zhao, Philip Kelso, Julie Calame, John J B Timmins, Elizabeth L I Wightman, Kai Peng, Alexander C Carpenter and 19 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Hugh D Goold *New South Wales Department of Primary Industries, Elizabeth Macarthur Agriculture Institute, Advanced Gene Technology Centre, Woodbridge Road, Menangle, NSW, 2568, Australia. hugh.goold@dpi.nsw.gov.au.
Heinrich Kroukamp *School of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia. heinrich.kroukamp@microbiogen.com.
Paige E ErpfSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Yu ZhaoInstitute for Systems Genetics, NYU Langone Health, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0003-4659-9832
Philip KelsoSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Julie CalameSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0009-0005-5247-275X
John J B TimminsSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Elizabeth L I WightmanSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0000-0002-9644-9317
Kai PengSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Alexander C CarpenterSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Briardo LlorenteSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0000-0002-3727-1395
Carmen HawthorneSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0009-0006-3480-9547
Samuel ClaySchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0009-0003-8794-2083
Niël van WykSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Elizabeth L DanielSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Fergus HarrisonSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Felix MeierSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Robert D WillowsSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Yizhi CaiManchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.ORCID http://orcid.org/0000-0003-1663-2865
Roy S K WalkerSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0000-0003-0960-4591
Xin XuSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0000-0002-5644-5397
Monica I EspinosaSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.
Giovanni StracquadanioSchool of Biological Sciences, The University of Edinburgh, Edinburgh, EH9 3BF, UK.ORCID http://orcid.org/0000-0001-9819-3645
Joel S BaderDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, 21218, USA.ORCID http://orcid.org/0000-0002-6020-4625
Leslie A MitchellInstitute for Systems Genetics, NYU Langone Health, New York, NY, 10016, USA.
Jef D BoekeInstitute for Systems Genetics, NYU Langone Health, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0001-5322-4946
Thomas C WilliamsSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia.ORCID http://orcid.org/0000-0002-0594-3441
Ian T PaulsenSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia. ian.paulsen@mq.edu.au.ORCID http://orcid.org/0000-0001-9015-9418
Isak S PretoriusSchool of Natural Sciences, and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, Australia. sakkie.pretorius@mq.edu.au.ORCID http://orcid.org/0000-0001-9127-3175

Funding

Department of Education and Training | Australian Research Council (ARC) CE200100029Department of Education and Training | Australian Research Council (ARC) DP200100717
6 · The paper itself

Abstract

The Sc2.0 global consortium to design and construct a synthetic genome based on the Saccharomyces cerevisiae genome commenced in 2006, comprising 16 synthetic chromosomes and a new-to-nature tRNA neochromosome. In this paper we describe assembly and debugging of the 902,994-bp synthetic Saccharomyces cerevisiae chromosome synXVI of the Sc2.0 project. Application of the CRISPR D-BUGS protocol identified defective loci, which were modified to improve sporulation and recover wild-type like growth when grown on glycerol as a sole carbon source when grown at 37˚C. LoxPsym sites inserted downstream of dubious open reading frames impacted the 5' UTR of genes required for optimal growth and were identified as a systematic cause of defective growth. Based on lessons learned from analysis of Sc2.0 defects and synXVI, an in-silico redesign of the synXVI chromosome was performed, which can be used as a blueprint for future synthetic yeast genome designs. The in-silico redesign of synXVI includes reduced PCR tag frequency, modified chunk and megachunk termini, and adjustments to allocation of loxPsym sites and TAA stop codons to dubious ORFs. This redesign provides a roadmap into applications of Sc2.0 strategies in non-yeast organisms.

Indexed as

Chromosomes, Artificial, YeastChromosomes, FungalSaccharomyces cerevisiaeSynthetic BiologyCRISPR-Cas SystemsGenome, FungalOpen Reading FramesRNA, TransferRNA, Transfer

Identifiers

PMID39833175
PMCPMC11747415

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.