The development of cell factories for the sustainable manufacturing of oleochemical is an enticing prospect. Using cell factories, it may be possible to produce a narrower range of FAs and oleochemicals from unspecific biomass as the feedstock, rather than unsustainable plant- or petroleum materials. Cell factories have the potential to address many of the challenges associated with plant-based supply chains. Cultivation of many microorganisms occurs over days and in closed environmental systems such as bioreactors, whereas plant production is often annually and regionally limited, and potentially allows more localized production, limiting the need for extensive transportation to maintain supply chains. In comparison with oleochemicals based on plant oils, cell factories allow greater consistency in product composition and purity profiles. Where plant-based production results in a mix of different acyl chain lengths (Carlsson, 2009), cell factories can be made compatible with renewable plant-based materials that can be grown on land not suitable for the cultivation of food crops. As previously noted, the use of edible oil in biochemical production has an influence on the global imbalance to the market demand and the food supply by their high prices, the reduction of food sources and the growth of commercial plant capacities. Thus, focus should be shifted to non-edible resources, which are not used in the human nutrition and could be grown in barren lands (Bozell & Petersen, 2010).
While the low abundance or yield of oleochemicals in wild microorganisms have rendered their isolation from such sources in many cases non-economically viable on an industrial scale, significant efforts have been put into finding genetic- and metabolic engineering strategies to increase production yields (Cravens et al., 2019; Ko et al., 2020; Nielsen & Keasling, 2016; T. Yu et al., 2018). The challenge is not only to design cell factories that can produce high yields, rates, and product titers of oleochemicals, but also to shorten the development time of each metabolic- and biosynthesis engineering design cycle, allowing cell factories to compete effectively with current petroleum-, and plant-based manufacturing processes as new markets develop.
The metabolism of natural producers with specific FA compositions are usually poorly understood, and they often lack immediate available tools for genetic modification available for model organism such as Saccharomyces cerevisiae and Escherichia coli. This makes them more difficult targets for engineering. Consequently, many new technologies depend on these well-known organisms by modifying existing biosynthesis pathways or introducing new ones (Calero & Nikel, 2019; Navarrete et al., 2020), showing great success in producing many highly-valuable target compounds such as complex opioids and vitamins (Galanie et al., 2015; Sun et al., 2019). Even as methods to produce and extract oleochemicals from microorganisms have been extensively explored (Marella et al., 2018; A.-Q. Yu et al., 2014) much of the current research has been focused on metabolic engineering to yield high-producing strains of one, or a few, number of structurally simple, low-molecular weight products such as such as aromatics, amines, terpenoids, terpenes, and esters (Calero & Nikel, 2019; Navarrete et al., 2020; Nielsen & Keasling, 2016). Although some natural products can be chemically synthesized - for example tunable synthesis of oleochemicals has been attempted using metal catalysts (Gollwitzer et al., 2017) - the complex structures of many of these compounds makes chemical synthesis either difficult or commercially infeasible (De Luca et al., 2012). The nature of biosynthesis in cell factories provide a promising route to generate a vast library of oleochemicals, even those difficult to extract, or not found in nature (Biermann et al., 2011; Nikolau et al., 2008).