Sarcosine, an N-methylated amino acid, shows potential as antipsychotic, and serves as building block for peptide-based drugs, and acts as detergent when acetylated. N-methylated amino acids are mainly produced chemically or by biocatalysis, with either low yields or high costs for co-factor regeneration. Corynebacterium glutamicum, which is used for the industrial production of amino acids for decades, has recently been engineered for production of N-methyl-L-alanine and sarcosine. Heterologous expression of dpkA in a C. glutamicum strain engineered for glyoxylate overproduction enabled fermentative production of sarcosine from sugars and monomethylamine. Here, mutation of an amino acyl residue in the substrate binding site of DpkA (DpkAF117L) led to an increased specific activity for reductive alkylamination of glyoxylate using monomethylamine and monoethylamine as substrates. Introduction of DpkAF117L into the production strain accelerated the production of sarcosine and a volumetric productivity of 0.16 g L−1 h−1 could be attained. Using monoethylamine as substrate, we demonstrated N-ethylglycine production with a volumetric productivity of 0.11 g L−1 h−1, which to the best of our knowledge is the first report of its fermentative production. Subsequently, the feasibility of using rice straw hydrolysate as alternative carbon source was tested and production of N-ethylglycine to a titer of 1.6 g L−1 after 60 h of fed-batch bioreactor cultivation could be attained.
Introduction: Adults aged ≥65 years contribute a large proportion of
influenza-related hospitalizations and deaths due to increased risk of
complications, which result in high medical costs and reduced
health-related quality of life (HRQoL). Although seasonal influenza
vaccines are recommended for older adults, the effectiveness of current
vaccines is dependent on several factors including strain matching and
recipient demographic factors. Objective: This systemic literature
review aimed to explore the economic and humanistic burden of influenza
in adults aged ≥65 years. Methods: An electronic database search was
conducted to identify studies assessing the economic and humanistic
burden of influenza, including influenza symptoms that impact the HRQoL
and patient related outcomes in adults aged ≥65 years. Studies were to
be published in English and conducted in Germany, France, Spain, and
Italy, United Kingdom, United States, Canada, China, Japan, Brazil,
Saudi Arabia, and South Africa. Results: Twenty-five studies reported on
the economic and humanistic burden of influenza in adults aged ≥65
years. Higher direct costs were reported for people at increased-risk of
influenza-related complications compared to those at low-risk. Lower
influenza-related total costs were found in those vaccinated with
adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to
high-dose trivalent influenza vaccine (TIV-HD). Older age was associated
with an increased occurrence and longer duration of certain influenza
symptoms. Despite the limited data identified for, results show that
influenza exerts a high humanistic and economic burden. in older adults.
Further research is required to confirm findings and to identify the
unmet needs of current vaccines.
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