Evidence map›Paper›PMID 38069118›Full record

ArticleInternational journal of molecular sciences2023

Simultaneous Improvement in the Thermostability and Catalytic Activity of Epoxidase Lsd18 for the Synthesis of Lasalocid A.

Ning Liu, Hongli Xiao, Yongjian Zang, Longji Zhou, Jun Mencius, Zhiwei Yang, Shu Quan, Xi Chen

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

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.9field-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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
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

8 authors at 4 institutions in 1 country.

Ning LiuKey Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China.
Hongli XiaoKey Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China.
Yongjian ZangMOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi'an Jiaotong University, Xi'an 710049, China.
Longji ZhouState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Jun MenciusState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.ORCID 0000-0001-5959-4737
Zhiwei YangMOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi'an Jiaotong University, Xi'an 710049, China.ORCID 0000-0001-6969-8177
Shu QuanState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.ORCID 0000-0002-6672-4947
Xi ChenKey Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China.ORCID 0000-0001-8295-2854
East China University of Science and Technology · CNMinistry of Education of the People's Republic of China · CNXi'an Jiaotong University · CNYunnan Normal University · CN

Funding

National Key Research and Development Program of China 2022YFC2106100Natural Science Foundation of China 21807088 and 32222049Open Funding Project of the State Key Laboratory of Bioreactor Engineering 2018OPEN05Open Project Program of State Key Laboratory of Cancer Biology CBSKL2022KF13 and CBSKL2022ZDKF07Projects of International Cooperation in Shaanxi Province of China 2023-GHYB-08Scholarship Program for Science and Technology Activities of Returned Overseas Scholars 2022-004
6 · The paper itself

Abstract

Enzymes used in the synthesis of natural products are potent catalysts, capable of efficient and stereoselective chemical transformations. Lsd18 catalyzes two sequential epoxidations during the biosynthesis of lasalocid A, a polyether polyketide natural product. We performed protein engineering on Lsd18 to improve its thermostability and catalytic activity. Utilizing structure-guided methods of FoldX and Rosetta-ddG, we designed 15 mutants of Lsd18. Screening of these mutants using thermal shift assay identified stabilized variants Lsd18-T189M, Lsd18-S195M, and the double mutant Lsd18-T189M-S195M. Trypsin digestion, molecular dynamic simulation, circular dichroism (CD) spectroscopy, and X-ray crystallography provided insights into the molecular basis for the improved enzyme properties. Notably, enhanced hydrophobic interaction within the enzyme core and interaction of the protein with the FAD cofactor appear to be responsible for its better thermostability.

Indexed as

LasalocidProteinsEnzyme StabilityMolecular Dynamics SimulationOxidoreductasesTemperatureepoxidaseLasalocidOxidoreductasesProteinscatalytic activityFoldXLsd18natural productRossetta-ddGthermostability

Identifiers

PMID38069118
PMCPMC10706071
OpenAlexW4389056473

What OpenQuestion 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 OpenQuestion graph.