Publications by authors named "Jonathan Humphreys"

Lanthipeptide synthetases are present in all domains of life. They catalyze a crucial step during lanthipeptide biosynthesis by introducing thioether linkages during posttranslational peptide modification. Lanthipeptides have a wide range of functions, including antimicrobial and morphogenetic activities.

View Article and Find Full Text PDF

Rational engineering of gas-fermenting bacteria for high yields of bioproducts is vital for a sustainable bioeconomy. It will allow the microbial chassis to renewably valorize natural resources from carbon oxides, hydrogen, and/or lignocellulosic feedstocks more efficiently. To date, rational design of gas-fermenting bacteria such as changing the expression levels of individual enzymes to obtain the desired pathway flux is challenging, because pathway design must follow a verifiable metabolic blueprint indicating where interventions should be executed.

View Article and Find Full Text PDF

Solventogenic clostridia represent a diverse group of anaerobic, spore-forming bacteria capable of producing acetone, butanol and ethanol through their unique biphasic metabolism. An intrinsic problem with these organisms however is their tendency to degenerate when repeatedly subcultured or when grown continuously. This phenomenon sees cells lose their ability to produce solvents and spores, posing a significant problem for industrial applications.

View Article and Find Full Text PDF

3-Hydroxybutyrate (3HB) is a product of interest as it is a precursor to the commercially produced bioplastic polyhydroxybutyrate. It can also serve as a platform for fine chemicals, medicines, and biofuels, making it a value-added product and feedstock. Acetogens non-photosynthetically fix CO into acetyl-CoA and have been previously engineered to convert acetyl-CoA into 3HB.

View Article and Find Full Text PDF

Using the Wood-Ljungdahl pathway, acetogens can nonphotosynthetically fix gaseous C molecules, preventing them from entering the atmosphere. Many acetogens can also grow on liquid C compounds such as formate and methanol, which avoid the storage and mass transfer issues associated with gaseous C compounds. Substrate redox state also plays an important role in acetogen metabolism and can modulate products formed by these organisms.

View Article and Find Full Text PDF

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production.

View Article and Find Full Text PDF

The sustainable production of chemicals from non-petrochemical sources is one of the greatest challenges of our time. CO release from industrial activity is not environmentally friendly yet provides an inexpensive feedstock for chemical production. One means of addressing this problem is using acetogenic bacteria to produce chemicals from CO, waste streams, or renewable resources.

View Article and Find Full Text PDF

Objective: V565 is a novel oral anti-tumor necrosis factor (TNF)-α domain antibody being developed for topical treatment of inflammatory bowel disease (IBD) patients. Protein engineering rendered the molecule resistant to intestinal proteases. Here we investigate the formulation of V565 required to provide gastro-protection and enable optimal delivery to the lower intestinal tract in monkeys.

View Article and Find Full Text PDF

is a spore-forming, anaerobic acetogen isolated from soil derived from east central Germany. The genome contains genes of the Wood-Ljungdahl pathway required for carbon fixation and genes involved in the biosynthesis of the amino acid pyrrolysine. The genome (5.

View Article and Find Full Text PDF

DSM 3132 is a strictly anaerobic, spore-forming and acetogenic bacterium, which was isolated from effluent of an alcohol distillation fermenter. The genome harbors genes involved in the Wood-Ljungdahl pathway for carbon fixation and several genes for glycerol metabolism. The genome (6.

View Article and Find Full Text PDF

Defensive chemistry is a key plant fitness trait, and the investigation of the expression of plant secondary metabolites across life stages is important in understanding the lifetime evolutionary selection pressures on a plant. The expression of genetic-based differences in foliar defensive chemistry, known to influence mammalian herbivore preferences, was studied across two contrasting life phases of the heteroblastic tree, Eucalyptus globulus. With plants from different subraces of E.

View Article and Find Full Text PDF