# Heterologous Production of Acrylic Acid: Current Challenges and Perspectives
## 1 Introduction  
Acrylic acid (AA), also known as 2-propenoic acid, propene acid, acroleic acid or vinylformic acid, is an unsaturated carboxylic acid with the chemical formula C\({}_{3}\)H\({}_{4}\)O\({}_{2}\) (Figure 1). AA is an industrial bulk chemical with diverse applications. This organic acid can be polymerized to form homopolymers (polyacrylamide acid) or can be co-polymerized with esters (e.g., butyl acrylate, ethyl acrylate, methyl acrylate) and other vinyl monomers [1]. AA and its derivatives are used to improve tackiness, hardness or elasticity, stability, durability and shelf-life in numerous polymer formulations. For example, superabsorbent polymers derived from AA (e.g., polyacrylic acid) are used in the production of diapers and sanitary pads. In addition, AA and its derivatives are used in adhesives, sealants, water treatment, plastic additives, textiles, paints, surface coatings, surfactants, and detergents, among others, due to all their mentioned beneficial properties [2]. The AA market was USD 13.35 billion in 2019 and was estimated to reach more than USD 20.2 billion by 2027 (CAGR of 5.7%) [3]. Due to the COVID-19 pandemic, the AA market in 2020 was only USD 12 billion and the projections were revised to USD 19.2 billion by 2030 (CAGR of 4.8%) [4]. Since approximately 30 % of the total market volume is related to sanitary or personal care products, such as adult diapers, the market is expected to continue growing as the geriatric population increases. Due to all its potential and market, AA is considered an interesting bulk chemical to be produced from biomass [1, 5, 6]. AA is mostly produced from the oxidation of propene obtained from crude oil. It can be produced in a one-step low-efficient process (50-60% yield) or, preferably and more recently, in a two-step more efficient process (\(\approx\)90%) having as an intermediary acrolein [1; 7]. Since petrochemicals are not renewable, AA cost increases as the supply of petroleum decreases. In addition to the raw materials used being non-renewable, the chemical processes are energy-intensive (high temperatures are used: 260-370 \({}^{\circ}\)C) [8; 9], use environmentally unfriendly catalysts and lead to high CO\({}_{2}\) emissions (3.3-7.7 kg CO\({}_{2}\)/kg AA) [10; 11]. Moreover, acrolein is toxic and explosive [11]. Therefore, it is important to develop more sustainable production processes. In the past decades, engineered microorganisms have been demonstrated to be a suitable option to produce numerous compounds with industrially relevant interest [12; 13; 14; 15; 16; 17] as the production processes are more environmentally friendly and have the potential to become more cost-effective. The use of synthetic biology and metabolic engineering approaches has allowed to construct more efficient strains able to produce heterologous compounds with higher concentrations and yields [18; 19; 20; 21; 22; 23; 24]. Tools such as clustered, regularly interspaced, short palindromic repeats-associated Cas9 (CRISPR-Cas9) have revolutionized the way microorganisms are designed as they make it possible to reconstruct complex metabolic pathways in a short period [25; 26]. Bearing all this in mind, research has recently focused on AA biosynthesis [27; 28; 29; 30; 31; 32; 33; 34]. In the past years, AA heterologous production has significantly evolved due to all the efforts made in the past focussing on the biosynthesis of 3-hydroxypropionic acid (3-HP), a possible intermediary compound in AA biosynthesis. 3-HP bio-based production has been intensively studied, and up to 125.93 g/L concentrations have already been obtained using different pathways and hosts [35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51; 52; 53]. This acid can be converted to AA by catalysis (dehydrogenation) or, more recently, by fermentation. In the past decades, various industrial parties, such as OPX Biotechnologies/Dow Chemical/Cargill/Novozymes/BASF, have constructed pilot plants for bio-based production of 3-HP and its chemical conversion to AA [54; 55; 56; 57; 43].