Genome-Driven Insights into Lactococcus sp. KTH0-1S Highlights Its Biotechnological Potential as a Cell Factory
by
, , , , and
Nisit Watthanasakphuban
1,
Hind Abibi
1,
Nuttakan Nitayapat
1,
Phitsanu Pinmanee
2,
Chollachai Klaysubun
3,
Nattarika Chaichana
3,
Komwit Surachat
3,*
and
Suttipun Keawsompong
1,* 1
Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Chatuchak, Bangkok 10900, Thailand
2
Enzyme Technology Research Team, National Center of Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani 12120, Thailand
3
Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
*
Authors to whom correspondence should be addressed.
Biology 2025, 14(10), 1323; https://doi.org/10.3390/biology14101323
Submission received: 19 August 2025
/
Revised: 20 September 2025
/
Accepted: 23 September 2025
/
Published: 25 September 2025
Simple Summary
This study investigates the bacterial strain Lactococcus sp. KTH0-1S as a potential alternative expression host and microbial cell factory. We confirmed that it is safe, carrying no harmful genes, and possesses traits that support survival in the digestive system and fermentation environments. Uniquely, the strain naturally produces nisin, which can act as an inducer for the NICE system, providing auto-induction properties that offer a simpler and more cost-effective alternative to conventional hosts. The strain also grows efficiently with nutrient support and can utilize a variety of sugars, including those from agricultural by-products. These characteristics make Lactococcus sp. KTH0-1S a promising next-generation probiotic and a versatile, food-grade microbial host for producing valuable proteins.
Abstract
The safety, genetic distinctiveness, and functional capabilities of Lactococcus sp. KTH0-1S, a strain isolated from Thai fermented shrimp (Kung-Som), were investigated to assess its potential as a next-generation probiotic and microbial cell factory. Whole-genome sequencing and multilocus sequence typing (MLST) analysis revealed that Lactococcus sp. KTH0-1S is a novel, phylogenetically distinct strain within the Lactococcus genus. Comprehensive in silico safety evaluation confirmed the absence of antimicrobial resistance genes and major virulence factors, supporting its suitability for food-grade applications. The genome encodes multiple probiotic-relevant traits, including stress tolerance (e.g., dnaK, clpP), adhesion and biofilm formation (e.g., gapA, luxS, glf2), and nutrient acquisition genes, enabling adaptation to gastrointestinal and fermentation environments. Notably, Lactococcus sp. KTH0-1S harbors a chromosomally encoded nisin Z biosynthesis gene cluster with auto-induction capability, providing a self-regulated and stable alternative to conventional plasmid-based NICE systems in Lactococcus lactis. The strain also exhibits nisin immunity, allowing tolerance to high nisin concentrations, thus supporting robust protein production. Genomic evidence and phenotypic assays confirmed a functional respiration metabolism activated by heme supplementation, enhancing biomass yield and culture stability. Furthermore, the presence of diverse CAZyme families (GHs, GTs, CEs) enables utilization of various carbohydrate substrates, including lignocellulosic and starchy agro-industrial residues. These properties collectively underscore Lactococcus sp. KTH0-1S as a safe, stable, and metabolically versatile candidate for probiotic applications and as a cost-effective, food-grade expression host for biotechnological production.
