Enhanced ε-Poly-L-Lysine Production in Streptomyces albulus through Multi-Omics-Guided Metabolic Engineering.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Streptomyces*/metabolism ; Streptomyces*/genetics ; Metabolic Engineering*/methods ; Polylysine*/biosynthesis ; Polylysine*/metabolism; Metabolome ; Transcriptome ; Metabolomics/methods ; Multiomics

Safe and eco-friendly preservatives are crucial to preventing food spoilage and illnesses, as foodborne diseases caused by pathogens result in approximately 600 million cases of illness and 420,000 deaths annually. ε-Poly-L-lysine (ε-PL) is a novel food preservative widely used in many countries. However, its commercial application has been hindered by high costs and low production. In this study, ε-PL's biosynthetic capacity was enhanced in Streptomyces albulus WG608 through metabolic engineering guided by multi-omics techniques. Based on transcriptome and metabolome data, differentially expressed genes (fold change >2 or <0.5; p < 0.05) and differentially expressed metabolites (fold change >1.2 or <0.8) were separately subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The integrative analysis of transcriptome, metabolome, and overexpression revealed the essential roles of isocitrate lyase, succinate dehydrogenase, flavoprotein subunit, diaminopimelate dehydrogenase, polyphosphate kinase, and polyP:AMP phosphotransferase in ε-PL biosynthesis. Subsequently, a strain with enhanced ATP supply, L-lysine supply, and ε-PL synthetase expression was constructed to improve its production. Finally, the resulting strain, S. albulus WME10, achieved an ε-PL production rate of 77.16 g/L in a 5 L bioreactor, which is the highest reported ε-PL production to date. These results suggest that the integrative analysis of the transcriptome and metabolome can facilitate the identification of key pathways and genetic elements affecting ε-PL synthesis, guiding further metabolic engineering and thus significantly enhancing ε-PL production. The method presented in this study could be applicable to other valuable natural antibacterial agents.

J Biosci Bioeng. 2021 Feb;131(2):147-152. (PMID: 33132038)
J Dairy Sci. 2019 Feb;102(2):1044-1058. (PMID: 30594364)
Bioresour Technol. 2021 Aug;333:125228. (PMID: 33957462)
Mar Drugs. 2020 Jan 11;18(1):. (PMID: 31940851)
Food Chem. 2022 Jun 15;379:132078. (PMID: 35063846)
Microb Cell Fact. 2023 Mar 14;22(1):51. (PMID: 36918890)
Nucleic Acids Res. 2022 Oct 28;50(19):11315-11330. (PMID: 36283692)
Microb Cell Fact. 2018 Jul 7;17(1):105. (PMID: 29981572)
Int J Mol Sci. 2022 Jan 08;23(2):. (PMID: 35054854)
Enzyme Microb Technol. 2016 Nov;93-94:70-78. (PMID: 27702487)
FEMS Microbiol Lett. 1997 Oct 15;155(2):223-9. (PMID: 9351205)
Bioresour Technol. 2023 Nov;387:129701. (PMID: 37604260)
Front Microbiol. 2024 Jan 24;15:1328321. (PMID: 38328422)
Microbiologyopen. 2019 May;8(5):e00728. (PMID: 30298553)
Microb Cell Fact. 2019 Apr 3;18(1):65. (PMID: 30943966)
Curr Microbiol. 2021 Jul;78(7):2640-2647. (PMID: 33991200)
Front Bioeng Biotechnol. 2020 Apr 22;8:288. (PMID: 32391338)
Microbiol Res. 2022 Sep;262:127101. (PMID: 35803058)
Crit Rev Biotechnol. 2018 Nov;38(7):1061-1076. (PMID: 29480038)
Bioresour Technol. 2021 Dec;341:125799. (PMID: 34425465)
Int J Mol Sci. 2021 Aug 23;22(16):. (PMID: 34445771)
Crit Rev Biotechnol. 2019 Dec;39(8):1031-1055. (PMID: 31544527)
J Sep Sci. 2024 Jan;47(1):e2300588. (PMID: 37942863)
J Biosci Bioeng. 2003;96(1):92-4. (PMID: 16233491)
Chem Commun (Camb). 2017 Apr 27;53(35):4803-4806. (PMID: 28405647)
Metab Eng. 2021 Sep;67:321-329. (PMID: 34329706)
Biotechnol Bioeng. 2012 Aug;109(8):2070-81. (PMID: 22392073)
Appl Microbiol Biotechnol. 2023 Apr;107(7-8):2611-2626. (PMID: 36882645)
Int J Mol Sci. 2014 Jul 09;15(7):12217-30. (PMID: 25007821)
ChemCatChem. 2019 Aug 7;11(15):3474-3489. (PMID: 31598184)
Microb Cell Fact. 2022 Apr 9;21(1):60. (PMID: 35397580)
Methods Mol Biol. 2013;985:447-58. (PMID: 23417817)
Int J Biol Macromol. 2024 Mar;262(Pt 1):129513. (PMID: 38262828)
Biotechnol Biofuels Bioprod. 2023 Apr 3;16(1):58. (PMID: 37013645)
J Ind Microbiol Biotechnol. 2018 Jun;45(6):393-404. (PMID: 29728854)
Bioengineered. 2022 Mar;13(3):5892-5902. (PMID: 35188864)
J Biosci Bioeng. 2020 May;129(5):558-564. (PMID: 31924510)
Food Res Int. 2023 Jan;163:112275. (PMID: 36596185)
Mol Gen Genet. 1988 Apr;212(1):105-11. (PMID: 3131636)
Bioprocess Biosyst Eng. 2018 Sep;41(9):1337-1345. (PMID: 29978263)
Appl Microbiol Biotechnol. 2007 Sep;76(4):873-82. (PMID: 17611754)
Appl Environ Microbiol. 2009 Jan;75(2):419-27. (PMID: 19047397)
Anal Biochem. 1972 Dec;50(2):569-74. (PMID: 4646067)
Nat Commun. 2021 Jun 11;12(1):3577. (PMID: 34117249)
J Microbiol Biotechnol. 2015 Nov;25(11):1819-26. (PMID: 26239011)
J Mol Microbiol Biotechnol. 2002 Jul;4(4):417-26. (PMID: 12125822)

2020YFA0907700 National Key R&D Program of China

Keywords: antimicrobial; metabolic engineering; multi-omics; preservatives; ε-Poly-L-lysine

25104-18-1 (Polylysine)

Streptomyces albus

Date Created: 20240727 Date Completed: 20240727 Latest Revision: 20240729

20250114

PMC11274744

10.3390/biom14070752

39062465