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Succinic acid (SA) is one of the top platform chemicals with huge applications in diverse sectors. The presence of two carboxylic acid groups on the terminal carbon atoms makes SA a highly functional molecule that can be derivatized into a wide range of products. The biological route for SA production is a cleaner, greener, and promising technological option with huge potential to sequester the potent greenhouse gas, carbon dioxide. The recycling of renewable carbon of biomass (an indirect form of CO2), along with fixing CO2 in the form of SA, offers a carbon-negative SA manufacturing route to reduce atmospheric CO2 load. These attractive attributes compel a paradigm shift from fossil-based to microbial SA manufacturing, as evidenced by several commercial-scale bio-SA production in the last decade. The current review article scrutinizes the existing knowledge and covers SA production by the most efficient SA producers, including several bacteria and yeast strains. The review starts with the biochemistry of the major pathways accumulating SA as an end product. It discusses the SA production from a variety of pure and crude renewable sources by native as well as engineered strains with details of pathway/metabolic, evolutionary, and process engineering approaches for enhancing TYP (titer, yield, and productivity) metrics. The review is then extended to recent progress on separation technologies to recover SA from fermentation broth. Thereafter, SA derivatization opportunities via chemo-catalysis are discussed for various high-value products, which are only a few steps away. The last two sections are devoted to the current scenario of industrial production of bio-SA and associated challenges, along with the author's perspective. [ABSTRACT FROM AUTHOR]

1,5-Pentanediol (1,5-PDO) is a high value-added chemical which is widely used as a monomer in the polymer industry. There are no natural organisms that could directly produce 1,5-PDO from renewable carbon sources. In this study, we report metabolic engineering of Escherichia coli for high-level production of 1,5-PDO from glucose via a cadaverine-derived pathway. In the newly proposed pathway, cadaverine can be converted to 1,5-PDO via 5-hydroxyvalerate (5-HV) by introducing only one heterologous enzyme in E. coli. Different endogenous genes of E. coli were screened and heterologous carboxylic acid reductase genes were tested to build a functional pathway. Compared to the previously reported pathways, the engineered cadaverine-based pathway has a higher theoretical yield (0.70 mol/mol glucose) and higher catalytic efficiency. By further combining strategies of pathway engineering and process engineering, we constructed an engineered E. coli strain that could produce 2.62 g/L 1,5-PDO in shake-flask and 9.25 g/L 1,5-PDO with a yield of 0.28 mol/mol glucose in fed-batch fermentation. The proposed new pathway and engineering strategies reported here should be useful for developing biological routes to produce 1,5-PDO for real application. • A cadaverine-based 1,5-PDO synthesis pathway was proposed for the first time. • Strategies to increase driving forces were adopted to increase the pathway efficiency. • Μetabolic engineering and process engineering were combined to increase strain performance. • An engineered strain can directly utilize glucose to produce 1,5-PDO with a titer of 9.25 g/L and a yield of 0.28 mol/mol. [ABSTRACT FROM AUTHOR]

Nitrilases represent a distinct class of enzymes that play a pivotal role in catalyzing the hydrolysis of nitrile compounds, leading to the formation of corresponding carboxylic acids. These enzymatic entities have garnered significant attention across a spectrum of industries, encompassing pharmaceuticals, agrochemicals, and fine chemicals. Moreover, their significance has been accentuated by mounting environmental pressures, propelling them into the forefront of biodegradation and bioremediation endeavors. Nevertheless, the natural nitrilases exhibit intrinsic limitations such as low thermal stability, narrow substrate selectivity, and inadaptability to varying environmental conditions. In the past decade, substantial efforts have been made in elucidating the structural underpinnings and catalytic mechanisms of nitrilase, providing basis for engineering of nitrilases. Significant breakthroughs have been made in the regulation of nitrilases with ideal catalytic properties and application of the enzymes for industrial productions. This review endeavors to provide a comprehensive discourse and summary of recent research advancements related to nitrilases, with a particular emphasis on the elucidation of the structural attributes, catalytic mechanisms, catalytic characteristics, and strategies for improving catalytic performance of nitrilases. Moreover, the exploration extends to the domain of process engineering and the multifarious applications of nitrilases. Furthermore, the future development trend of nitrilases is prospected, providing important guidance for research and application in the related fields. • The substrate promiscuity of nitrilases enhanced their versatility. • The catalytic characteristics and improvement strategies of nitrilase are overviewed. • The process engineering expanded the application scenarios of nitrilase. • The industrial and environmental applications of nitrilase are summarized. • Challenges and future research directions of nitrilase engineering are discussed. [ABSTRACT FROM AUTHOR]

Covering: up to the end of 2020 Organic acids, as building block compounds, have been widely used in food, pharmaceutical, plastic, and chemical industries. Until now, chemical synthesis is still the primary method for industrial-scale organic acid production. However, this process encounters some inevitable challenges, such as depletable petroleum resources, harsh reaction conditions and complex downstream processes. To solve these problems, microbial cell factories provide a promising approach for achieving the sustainable production of organic acids. However, some key metabolites in central carbon metabolism are strictly regulated by the network of cellular metabolism, resulting in the low productivity of organic acids. Thus, multiple metabolic engineering strategies have been developed to reprogram microbial cell factories to produce organic acids, including monocarboxylic acids, hydroxy carboxylic acids, amino carboxylic acids, dicarboxylic acids and monomeric units for polymers. These strategies mainly center on improving the catalytic efficiency of the enzymes to increase the conversion rate, balancing the multi-gene biosynthetic pathways to reduce the byproduct formation, strengthening the metabolic flux to promote the product biosynthesis, optimizing the metabolic network to adapt the environmental conditions and enhancing substrate utilization to broaden the substrate spectrum. Here, we describe the recent advances in producing C2–C6 organic acids by metabolic engineering strategies. In addition, we provide new insights as to when, what and how these strategies should be taken. Future challenges are also discussed in further advancing microbial engineering and establishing efficient biorefineries. [ABSTRACT FROM AUTHOR]