Evidence map›Paper›PMID 30782164›Full record

ArticleMicrobial cell factories2019

Engineering of leucine-responsive regulatory protein improves spiramycin and bitespiramycin biosynthesis.

Zhili Lu, Xiaoting Zhang, Jianlu Dai, Yiguang Wang, Weiqing He

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Microbial cell factories, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
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

16 citing papers in PubMed, 24 citations in OpenAlex.

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  16. Synthetic biology enabling access to designer polyketides.Current opinion in chemical biology · 2020
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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

5 authors at 2 institutions in 1 country.

Zhili LuState Key Laboratory of Respiratory Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Xiaoting ZhangNHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, No. 1 Tian Tan Xi Li, Beijing, 100050, People's Republic of China.
Jianlu DaiNHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, No. 1 Tian Tan Xi Li, Beijing, 100050, People's Republic of China.
Yiguang WangNHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, No. 1 Tian Tan Xi Li, Beijing, 100050, People's Republic of China.
Weiqing HeNHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, No. 1 Tian Tan Xi Li, Beijing, 100050, People's Republic of China. heweiqing@imb.pumc.edu.cn.ORCID http://orcid.org/0000-0002-9621-3769
Chinese Academy of Medical Sciences & Peking Union Medical College · CNGuangzhou Institutes of Biomedicine and Health · CN

Funding

Chinese Academy of Medical Sciences 2017-I2M-1-012National Foundation for Science and Technology Development 2014ZX09201003-002National Natural Science Foundation of China 81773617
6 · The paper itself

Abstract

backgroundBitespiramycin (BT) is produced by recombinant spiramycin (SP) producing strain Streptomyces spiramyceticus harboring a heterologous 4″-O-isovaleryltransferase gene (ist). Exogenous L-Leucine (L-Leu) could improve the production of BT. The orf2 gene found from the genomic sequence of S. spiramyceticus encodes a leucine-responsive regulatory protein (Lrp) family regulator named as SSP_Lrp. The functions of SSP_Lrp and L-Leu involved in the biosynthesis of spiramycin (SP) and BT were investigated in S. spiramyceticus.

resultsSSP_Lrp was a global regulator directly affecting the expression of three positive regulatory genes, bsm23, bsm42 and acyB2, in SP or BT biosynthesis. Inactivation of SSP_Lrp gene in S. spiramyceticus 1941 caused minor increase of SP production. However, SP production of the ΔSSP_Lrp-SP strain containing an SSP_Lrp deficient of putative L-Leu binding domain was higher than that of S. spiramyceticus 1941 (476.2 ± 3.1 μg/L versus 313.3 ± 25.2 μg/L, respectively), especially SP III increased remarkably. The yield of BT in ΔSSP_Lrp-BT strain was more than twice than that in 1941-BT. The fact that intracellular concentrations of branched-chain amino acids (BCAAs) decreased markedly in the ΔSSP_Lrp-SP demonstrated increasing catabolism of BCAAs provided more precursors for SP biosynthesis. Comparative analysis of transcriptome profiles of the ΔSSP_Lrp-SP and S. spiramyceticus 1941 found 12 genes with obvious differences in expression, including 6 up-regulated genes and 6 down-regulated genes. The up-regulated genes are related to PKS gene for SP biosynthesis, isoprenoid biosynthesis, a Sigma24 family factor, the metabolism of aspartic acid, pyruvate and acyl-CoA; and the down-regulated genes are associated with ribosomal proteins, an AcrR family regulator, and biosynthesis of terpenoid, glutamate and glutamine.

conclusionSSP_Lrp in S. spiramyceticus was a negative regulator involved in the SP and BT biosynthesis. The deletion of SSP_Lrp putative L-Leu binding domain was advantageous for production of BT and SP, especially their III components.

Indexed as

Escherichia coliEscherichia coli ProteinsGenetic EngineeringLeucineLeucine-Responsive Regulatory ProteinSpiramycinStreptomycesbitespiramycinEscherichia coli ProteinsLeucineLeucine-Responsive Regulatory ProteinSpiramycinBitespiramycinBranched-chain amino acidsLeucine-responsive regulatory proteinSpiramycin

Identifiers

PMID30782164
PMCPMC6379999
OpenAlexW2922769190

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.