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Complex waste stream valorization through combined enzymatic hydrolysis and catabolic assimilation by Pseudomonas putida.
Trends Biotechnol
March 2025
Manchester Institute of Biotechnology (MIB), Department of Chemistry, University of Manchester, Manchester, M1 7DN, UK. Electronic address:
Biogenic waste-derived feedstocks for production of fuels, chemicals, and materials offer great potential supporting the transition to net-zero and greater circularity. However, such feedstocks are heterogeneous and subject to geographical and seasonal variability. Here, we show that, through careful strain selection and metabolic engineering, Pseudomonas putida can be employed to permit efficient co-utilization of highly heterogeneous substrate compositions derived from hydrolyzed mixed municipal-like waste fractions (food, plastic, organic, paper, cardboard, and textiles) for growth and synthesis of exemplar bioproducts.
View Article and Find Full Text PDFKilo-Scale GMP Synthesis of Renewable Semisynthetic Vaccine-Grade Squalene.
Org Process Res Dev
December 2023
Amyris Inc, 5885 Hollis St, Suite 100, Emeryville, CA 94608, USA.
Emulsions of the triterpene squalene ((6,10,14,18)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, CAS 111-02-4) have been used as adjuvants in influenza vaccines since the 1990s. Traditionally sourced from shark liver oil, the overfishing of sharks and concomitant reduction in the oceanic shark population raises sustainability issues for vaccine adjuvant grade squalene. We report a semisynthetic route to squalene meeting current pharmacopeial specifications for use in vaccines that leverages the ready availability of -β-farnesene ((6)-7,11-dimethyl-3-methylene-1,6,10-dodecatriene, CAS 18794-84-8), manufactured from sustainable sugarcane via a yeast fermentation process.
View Article and Find Full Text PDFThe prFMNH-binding chaperone LpdD assists UbiD decarboxylase activation.
J Biol Chem
February 2024
Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. Electronic address:
The UbiD enzyme family of prenylated flavin (prFMN)-dependent reversible decarboxylases is near ubiquitously present in microbes. For some UbiD family members, enzyme activation through prFMNH binding and subsequent oxidative maturation of the cofactor readily occurs, both in vivo in a heterologous host and through in vitro reconstitution. However, isolation of the active holo-enzyme has proven intractable for others, notably the canonical Escherichia coli UbiD.
View Article and Find Full Text PDFEfficient NADPH-dependent dehalogenation afforded by a self-sufficient reductive dehalogenase.
J Biol Chem
September 2023
Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. Electronic address:
Reductive dehalogenases are corrinoid and iron-sulfur cluster-containing enzymes that catalyze the reductive removal of a halogen atom. The oxygen-sensitive and membrane-associated nature of the respiratory reductive dehalogenases has hindered their detailed kinetic study. In contrast, the evolutionarily related catabolic reductive dehalogenases are oxygen tolerant, with those that are naturally fused to a reductase domain with similarity to phthalate dioxygenase presenting attractive targets for further study.
View Article and Find Full Text PDFSemi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions.
NPJ Vaccines
February 2023
Access to Advanced Health Institute, formerly Infectious Disease Research Institute, Seattle, WA, USA.
Synthetic biology has allowed for the industrial production of supply-limited sesquiterpenoids such as the antimalarial drug artemisinin and β-farnesene. One of the only unmodified animal products used in medicine is squalene, a triterpenoid derived from shark liver oil, which when formulated into an emulsion is used as a vaccine adjuvant to enhance immune responses in licensed vaccines. However, overfishing is depleting deep-sea shark populations, leading to potential supply problems for squalene.
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