Biology subjects

Yu, L.-S.

Publications and source records attributed to Yu, L.-S..

4 recordsLinked to original sources

bioRxiv2026

Tailoring Precise Genomic Integration Toward Isolate-to-Industry Strain Development for Scalable High-Titer Production of Polyhydroxyalkanoate

Halophilic chassis has emerged as a promising biomanufacturing platform for industrial polyhydroxyalkanoate (PHA) production. However, challenges still remain in improving the production capacity, scalability and robustness, thereby lowering cost to meet market demands. Here, a high-performing halophilic strain Halomonas LY03 was isolated with over 38% glucose- to-PHA conversion rate and broad non-grain substrate utilization capability. Multidimensional tools, including algorithm-guided high-expression neutral integration site (HENIS) screening toolkit designated SiteSeek, stop codon (TAA)-dependent enhancement of gene expression and recombinase-mediated large-fragment (> 9 kb) genomic integration, were then developed to enable precise, efficient and interference-free genomic integrative expression. Using these tools, various chromosomally engineered strains were rapidly constructed to achieve high-level production of poly-3-hydroxybutyrate (PHB, 151 g L-{superscript 1}) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB, 139 g L-{superscript 1}) under high cell-density fermentation (up to 186 g L-1 cell dry weight) in a 5-L bioreactor. Scalability was demonstrated at 2-m3 and 20-m3 industry-scale fermentations, yielding up to 134 g L-{superscript 1} PHB and 127 g L-{superscript 1} P34HB (6.1 mol% 4HB). Building on the proven robustness, a two-stage continuous fermentation (TCF) process was developed using a twin-bioreactor system at 5-L and 20-m3 scales, where stable and sustained PHA production lasted over 260 h and 160 h, respectively. Techno-economic analysis revealed a substantial cost-reduction space of 48% compared with conventional fed-batch process. This study demonstrates a successful paradigm for engineering a newly isolated strain toward robust, high-titer and cost-competitive PHA production across lab-to-industry scales.

synthetic biology↗

bioRxiv2026

Engineering xylose metabolism for diverse polyhydroxyalkanoates synthesis in Halomonas TD

Engineering the biosynthesis of fully biodegradable polyhydroxyalkanoates (PHAs) from non-food and renewable feedstocks like lignocellulose is becoming an attractive strategy for sustainable biomanufacturing. However, the efficiency and diversity of PHA synthesis from lignocellulosic hydrolysate (LH), mainly containing glucose and xylose, still remains challenge. Here, Halomonas TD, a cost-effective PHA-producing chassis, was developed to utilize glucose and xylose (or LH) for effective production of poly-3-hydroxybutyrate (PHB) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] by engineering the phosphoketolase pathway-dependent xylose metabolism in the genome, yielding 50.1 g L-1 PHB and 42.6 g L-1 P(3HB-co- 11.4 mol% 4HB) under fed-batch condition. Subsequently, the introduction of Weimberg pathway was found be able to synthesize terpolymer consisting of 3-hydroxybutyrate (3HB), 4-hydroxybutyrate (4HB) and 3-hydroxyvalerate (3HV), namely [P(3HB-co-4HB-co-3HV)], from glucose and xylose only due to the isoenzyme activity of keto-acid decarboxylase encoded by kivD, which converts xylose-derived intermediate 2,5-dioxopentanoate and -ketoglutarate into butanedial (4HB synthesis) and 2-ketobutyrate (3HV synthesis), respectively. Finally, a tailored-made xylose-induced system was constructed to achieve exquisite xylose transmembrane transportation control for improved synthesis of terpolymer P(3HB-co-4.5 mol% 4HB-co- 3.0 mol% 3HV), reaching to 6.3 g L-1 under shake-flask condition, together with the co-expression of fine-tuned phosphoketolase and Weimberg pathways. This study provides a feasible and sustainable alternative for lignocellulosic resources valorization powered by the engineered Halomonas TD capable of efficient xylose utilization and diverse PHAs synthesis.

bioengineering↗

bioRxiv2019

Quantitative and rapid Plasmodium falciparum malaria diagnosis and artemisinin-resistance detection using a CMOS Lab-on-Chip platform

Early and accurate diagnosis of malaria and drug-resistance is essential to effective disease management. Available rapid malaria diagnostic tests present limitations in analytical sensitivity, drug-resistant testing and/or quantification. Conversely, diagnostic methods based on nucleic acid amplification stepped forwards owing to their high sensitivity, specificity and robustness. Nevertheless, these methods commonly rely on optical measurements and complex instrumentation which limit their applicability in resource-poor, point-of-care settings. This paper reports the specific, quantitative and fully-electronic detection of Plas-modium falciparum, the predominant malaria-causing parasite worldwide, using a Lab-on-Chip platform developed in-house. Furthermore, we demonstrate on-chip detection of C580Y, the most prevalent single-nucleotide polymorphism associated to artemisinin-resistant malaria. Real-time non-optical DNA sensing is facilitated using Ion-Sensitive Field-Effect Transistors, fabricated in unmodified complementary metal-oxide-semiconductor technology, coupled with loop-mediated isothermal amplification. This work holds significant potential for the development of a fully portable and quantitative malaria diagnostic that can be used as a rapid point-of-care test.

bioengineering↗

bioRxiv2017

Sublethal effects of the neonicotinoid insecticide thiamethoxam on the transcriptome of the honeybee (Apis mellifera)

Neonicotinoid insecticides are now the most widely used insecticides in the world. Previous studies have indicated that sublethal doses of neonicotinoids impair learning, memory capacity, foraging and immunocompetence in honeybees (Apis mellifera). Despite this, few studies have been carried out on the molecular effects of neonicotinoids. In this study, we focus on the second-generation neonicotinoid thiamethoxam, which is currently widely used in agriculture to protect crops. Using high-throughput RNA-Seq, we investigated the transcriptome profile of honeybees after subchronic exposure to thiamethoxam (10 ppb) over 10 days. In total, 609 differentially-expressed genes (DEGs) were identified, of which 225 were up-regulated and 384 were down-regulated. The functions of some DEGs were identified, and GO enrichment analysis showed that the enriched DEGs were mainly linked to metabolism, biosynthesis and translation. KEGG pathway analysis showed that thiamethoxam affected biological processes including ribosomes, the oxidative phosphorylation pathway, tyrosine metabolism pathway, pentose and glucuronate interconversions and drug metabolism. Overall, our results provide a basis for understanding the molecular mechanisms of the complex interactions between neonicotinoid insecticides and honeybees.\n\nSummary statementNR1, Cyp6as5, nAChRa9 and nAChR{beta}2 were up-regulated in honeybees exposed to thiamethoxam, while CSP3, Obp21, defensin-1, Mrjp1, Mrjp3 and Mrjp4 were down-regulated.

molecular biology↗