Growing environmental concern sparks renewed interest in the sustainable production of (bio)materials that can replace oil‐derived goods. Polyhydroxyalkanoates (PHAs) are isotactic polymers that play a critical role in the central metabolism of producer bacteria, as they act as dynamic reservoirs of carbon and reducing equivalents. PHAs continue to attract industrial attention as a starting point toward renewable, biodegradable, biocompatible, and versatile thermoplastic and elastomeric materials. Pseudomonas species have been known for long as efficient biopolymer producers, especially for medium‐chain‐length PHAs. The surge of synthetic biology and metabolic engineering approaches in recent years offers the possibility of exploiting the untapped potential of Pseudomonas cell factories for the production of tailored PHAs. In this article, an overview of the metabolic and regulatory circuits that rule PHA accumulation in Pseudomonas putida is provided, and approaches leading to the biosynthesis of novel polymers (e.g., PHAs including nonbiological chemical elements in their structures) are discussed. The potential of novel PHAs to disrupt existing and future market segments is closer to realization than ever before. The review is concluded by pinpointing challenges that currently hinder the wide adoption of bio‐based PHAs, and strategies toward programmable polymer biosynthesis from alternative substrates in engineered P. putida strains are proposed.
A proper response to elevated extracellular calcium levels helps to most organisms to keep this secondary messenger under strict control, thereby preventing inadequate activation or inhibition of many regulatory activities into cells. In fungi, the calcineurin responsive zinc-finger Crz1/CrzA transcription factor transduces calcium signaling to gene expression. In Aspergillus nidulans, absence of CrzA activity leads to alkaline pH sensitivity and loss of tolerance to high levels of extracellular calcium. Disruption of calcium uptake mechanisms or the presence of high levels of Mg 2+ partially suppresses this calcium-sensitive phenotype of null crzA strain. The effects of Mg 2+ on CrzA phosphorylation and perturbations that reduce calcineurin phosphatase activity on CrzA demonstrate that the calcium sensitive phenotype of null crzA strain is a consequence of up-regulated calcineurin activity under calciuminduced conditions.
Invasive aspergillosis (IA) is one of the most severe forms of fungi infection. IA disease is mainly due to Aspergillus fumigatus, an air-borne opportunistic pathogen. Mortality rate caused by IA is still very high (50-95%), because of difficulty in early diagnostics and reduced antifungal treatment options, thus new and efficient drugs are necessary. The aim of this work is, using Aspergillus nidulans as non-pathogen model, to develop efficient drugs to treat IA. The recent discovered role of glycogen synthase kinase-3 homologue, GskA, in A. fumigatus human infection and our previous experience on human GSK-3 inhibitors focus our attention on this kinase as a target for the development of antifungal drugs. With the aim to identify effective inhibitors of colonial growth of A. fumigatus we use A. nidulans as an accurate model for in vivo and in silico studies. Several well-known human GSK-3β inhibitors were tested for inhibition of A. nidulans colony growth. Computational tools as docking studies and binding site prediction was used to explain the different biological profile of the tested inhibitors. Three of the five tested hGSK3β inhibitors are able to reduce completely the colonial growth by covalent bind to the enzyme. Therefore these compounds may be useful in different applications to eradicate IA.
Despite large research efforts devoted to understanding the flexible metabolism of
Pseudomonas
beyond the role of key regulatory players, the metabolic basis powering the dynamic control of its biological fitness under disturbance conditions remains largely unknown. Among other metabolic hubs, the so-called PHA cycle, involving simultaneous synthesis and degradation of PHAs, is emerging as a pivotal metabolic trait powering metabolic robustness and resilience in this bacterial group.
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