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Comparative genomic and transcriptomic analysis guides to further enhance the biosynthesis of erythromycin by an overproducer
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  • Xiaobo Li,
  • Xiang Ke,
  • Ju Chu,
  • Lijia Qiao,
  • Yufei Sui
Xiaobo Li
East China University of Science and Technology

Corresponding Author:[email protected]

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Xiang Ke
East China University of Science and Technology
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Ju Chu
State Key Laboratory of Bioreactor Engineering
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Lijia Qiao
East China University of Science and Technology
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Yufei Sui
East China University of Science and Technology
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Abstract

Omics approaches have been applied to understand the boosted productivity of natural products by industrial high-producing microorganisms. Here, with the updated genome sequence and transcriptomic profiles derived from high-throughput sequencing, we exploited comparative omics analysis to further enhance the biosynthesis of erythromycin in an industrial overproducer, Saccharopolyspora erythraea HL3168 E3. By comparing the genome of E3 with the wild type NRRL23338, we identified fragment deletions inside 56 coding sequences and 255 single nucleotide polymorphisms over the genome of E3. Substantial numbers of genomic variations were observed in genes responsible for pathways which were interconnected to the biosynthesis of erythromycin by supplying precursors/cofactors or by signal transduction. Through comparative transcriptomic analysis, L-glutamine/L-glutamate and 2-oxoglutarate were identified as reporter metabolites. Around the node of 2-oxoglutarate, genomic mutations were also observed. Furthermore, the transcriptomic data suggested that genes involved in the biosynthesis of erythromycin were significantly up-regulated constantly, whereas some genes in biosynthesis clusters of other secondary metabolites contained nonsense mutations and were expressed at extremely low levels. Based on the omics association analysis, readily available strategies were proposed to engineer E3 by simultaneously overexpressing sucB (coding for 2-oxoglutarate dehydrogenase E2 component) and sucA (coding for 2-oxoglutarate dehydrogenase E1 component), which increased the erythromycin titer by 71% compared to E3 in batch culture. This work provides more promising molecular targets to engineer for enhanced production of erythromycin by the overproducer.
15 Oct 2021Submitted to Biotechnology and Bioengineering
16 Oct 2021Submission Checks Completed
16 Oct 2021Assigned to Editor
18 Oct 2021Reviewer(s) Assigned
10 Nov 2021Review(s) Completed, Editorial Evaluation Pending
10 Nov 2021Editorial Decision: Revise Major
21 Dec 20211st Revision Received
24 Dec 2021Submission Checks Completed
24 Dec 2021Assigned to Editor
26 Dec 2021Reviewer(s) Assigned
10 Jan 2022Review(s) Completed, Editorial Evaluation Pending
10 Jan 2022Editorial Decision: Revise Minor
19 Jan 20222nd Revision Received
19 Jan 2022Submission Checks Completed
19 Jan 2022Assigned to Editor
23 Jan 2022Reviewer(s) Assigned
28 Jan 2022Review(s) Completed, Editorial Evaluation Pending
28 Jan 2022Editorial Decision: Accept
Jun 2022Published in Biotechnology and Bioengineering volume 119 issue 6 on pages 1624-1640. 10.1002/bit.28059