Thermophilic microorganisms, capable of thriving under high temperatures, are emerging as key platforms for next-generation industrial biotechnology (NGIB), driving innovations in lignin biorefining, bioplastics synthesis, biodiesel production, and environmental remediation. Enzymes derived from thermophilic microorganisms, thermozymes, exhibit remarkable stability and efficiency under extreme conditions, making them highly suitable for diverse industrial applications. This review highlights recent advances in leveraging thermophilic microorganisms and thermozymes for high-temperature catalysis, focusing on their economic and environmental benefits. It also emphasizes progress in high-throughput screening and artificial intelligence (AI), which have revolutionized the bioprospecting, engineering, and application potential of thermozymes. Challenges and potential solutions for industrial implementation of high-temperature catalytic platforms are also discussed, highlighting their transformative impact on sustainable biotechnology.
The high molecular weight, hydrophobicity, and strong chemical bonds of petroleum-based synthetic plastics make them highly resistant to both abiotic and microbial degradation. This resistance plays a significant role in the growing problem of “white pollution” where the accumulation of plastic waste has become a major environmental issue worldwide. Currently, plastic waste management relies largely on landfill disposal and incineration, with only about 20% of plastic waste being recycled. However, both methods create secondary environmental risks, such as contamination of groundwater, soil, air, and oceans. Therefore, developing a sustainable and efficient approach for recycling and reusing plastic waste is essential for tackling plastic pollution and promoting a circular plastic economy. One promising solution involves utilizing microorganisms and enzymes to break down plastics into oligomers or monomers, which can then be transformed into valuable chemicals. This method provides a more environmentally friendly and milder alternative to conventional waste management techniques. This review explores recent progress in biodepolymerization and biotransformation processes for plastic waste, including the identification of plastic-degrading microorganisms and enzymes, the creation of microbial consortia and enzyme mixtures, an investigation into the mechanisms of plastic depolymerization, and the conversion of degradation products into useful materials such as chemicals, energy, and other resources. Despite these advancements, several challenges remain, such as the limited availability of effective degradation enzymes, low degradation efficiency, and difficulties in utilizing the breakdown products. However, emerging technologies in synthetic biology, such as high-throughput screening, evolutionary metabolic engineering, and bioinformatics to study catalytic mechanisms of degradation enzymes, offer promising solutions to address these issues. By improving enzyme design, optimizing microbial consortia interactions, and developing efficient metabolic pathways for plastic degradation products, these innovations could greatly enhance plastic biodegradation. These advancements hold the potential to provide environmentally sustainable, economically feasible, and technically viable solutions for promoting a circular plastic economy, particularly in countries like China.
Microbial cell factories, akin to “chips” in biomanufacturing, concentrate the most intricate scientific challenges, technical bottlenecks, and densest intellectual property. However, despite extensive efforts in rational engineering, the inherent complexity of biological systems and the limited knowledge of their underlying mechanisms still incur substantial trial-and-error costs. This Perspective seeks to explore the potential of a prior-knowledge-independent approach for optimizing microbial cell factory phenotypes. We discuss the feasibility of stepwise genotypic navigation in genome engineering and emphasize its ability to generate high-quality genotype–phenotype association data, thereby advancing AI-assisted genome modeling and further enabling precision-guided optimization.
The production of glycerol as a major by-product during yeast-based bioethanol fermentation arises directly from the need to re-oxidize excess NADH, which reduces conversion efficiency. In this study, an optimized Cas9-based genome editing method was performed to develop a mixotrophic CO2-fixing industrial Saccharomyces cerevisiae by heterologous expression of ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO form Pseudomonas sp.) and phosphoribulokinase (PRK form Spinach). Additionally, the gene encoding alcohol dehydrogenase (ADH2) responsible for converting ethanol to acetaldehyde was deleted, while the great wall-family protein kinase Rim15 gene was overexpressed to facilitate the reduction in glycerol content. The resulting CO2-fixing yeast M-2 led to a 21.5% reduction of the by-product glycerol in corn mash fermentation cultures at 39 ℃. Moreover, we established a novel gene mutators mediated genome-wide mutations system that accumulates distinct mutations in the industrial S. cerevisiae strains under the stress conditions to improve the robustness in the S. cerevisiae strains efficiently.
The biological production of n-butanol has seen renewed interest due to the need for the production of sustainable aviation fuel, for which n-butanol serves as a direct precursor. However, biological production of this alcohol is still limited by the fermentation’s low titers and low yields. Many approaches have been taken to increase n-butanol production, such as using alternative host organisms, utilizing heterologous enzymes for acid reduction and cofactor regeneration, and protein engineering of critical enzymes in the n-butanol production metabolic pathway. This review highlights key achievements made in each of these areas and shows the potential for these approaches in increasing n-butanol production. The review closes by pinpointing the challenges and limitations in these approaches and recommends that the ultimate approach to n-butanol production should inevitably utilize noncanonical redox cofactors to drive metabolic flux for butanol biosynthesis from glucose.
