Microalgae (including cyanobacteria) are predominantly unicellular photosynthetic organisms which constitute the base of aquatic food webs. As an ancestor of plants with billions of years of evolutionary history, they distinctively adapted to extreme habitats and developed massive phylogenetic and biochemical diversity [1,2]. They have colonized almost all biotopes and been acclimated to severe environments, living in salt marshes, deserts or environments with very low light [3]. Not only do some microalgae tolerate hostile environmental conditions but also need these conditions to thrive. As a consequence of diurnal, seasonal, vertical and geographic variations plus fluctuations in nutrient availability, temperature, light and other factors, the distribution and metabolic activities of microalgae and the biomolecules they produce may be significantly more heterogeneous than previously believed [2].

In recent decades, microalgae emerged as new, attractive, promising and scalable platforms for the production of some biomolecules [4]. Among these biomolecules, some primary and secondary metabolites, such as carotenoids and proteins, were already commercialized as customer products, which intrigues further R&D to prospect more bioproducts from microalgae [5]. The efforts of developing these bioproducts from microalgae are underway, but with a number of constraints including: low product yield, slow growth rates, high cost of production facility, frequent contamination, high cost of harvesting, high energy consumption of cell lysis and complicated process of extraction of the desired metabolites [6]. The primary focus of the process development is to increase the yield of these biomolecules and the growth rates of microalgae. The evolution of genetic engineering technologies of microalgae progressed considerably for the past decades, and the research results obtained helped to boost the economic viability of commercial microalgal productions. This purpose of this study is to summarize the recent development and the emerging trends of molecular biotechnology applied to microalgae to increase the cells’ growth performance as well as to improve the synthesis rates of primary and secondary metabolites from this valuable group of organisms.

Microalgae could be prokaryotic or eukaryotic and are phylogenetically very diverse. The eukaryotic microalgae might be traced back 1.9 × 10⁹ years and are much younger than the cyanobacteria with 2.7 × 10⁹ years of phylogenetic history [1]. After the progenitor of the algae arose through an endosymbiosis with cyanobacterium, two evolutionary lines appeared simultaneously, namely green and red algae. These two lines acquired a number of various distinctive characteristics. Further groups of algae did not appear until much later through the secondary endosymbiosis, while the green and red algae are transformed into plastids in a eukaryotic host. This process gave rise to the heterokont algae, the Dinoflagellates, the Cryptophytes and the Euglenida [1]. Because of several biochemical and cellular disparities, two principal groups of green microalgae are identified: the Chlorophyta and the Conjugaphyta. While the second group is nearly five times larger than the Chlorophyta, none of the Conjugaphyta is yet applied for biotechnological engineering [1].

Algal diversity is very large and represents an almost unexploited natural resource. In accordance with some early assessments, there might be tens of thousands to millions of microalgae species, only a tiny fraction of which were isolated or described [2]. A more accurate number of estimation might be 72,500 species, which is still roughly twice as that of plants [7]. In recent decades, huge microalgal collections were generated by researchers from various countries. An example is the collection of freshwater microalgae from the Coimbra College (Coimbra, Portugal), considered to be among the largest in the world, with over 4000 different strains with more than 1000 species. The collection mirrors the broad array of microalgae ready to be used in various applications [8]. Microalgae are therefore a group that is not well studied in biotechnology terms. Of the great variety of microalgal species thought to exist, just some thousands of strains are preserved in collections around the world, with just some hundreds explored for chemical composition and only tens cultivated in manufacturing (tons per year) [9].

The wide variability of microalgae provides a large range of potential applications as source of feeding, stock of biomaterials and bioreactor of biotechnologically important molecules [8,10]. This diverse phylogeny is also expressed in a large biochemical diversity of pigments, photosynthetic storage products, mucilage materials, fatty acids, oils and hydrocarbons, sterols and secondary bioactive compounds, relating secondary metabolites [2,11]. Except for having a specific compound available that makes these organisms interesting, their diversity and the possibility of harvesting and cultivating under various conditions allows for using them as natural bioreactors for producing multiple chemicals through biorefinery or integrated processes [11].

The use of microalgae by humans was practiced since many years as food, feed, medicines and fertilizers. In the 14th century, the Aztecs harvested Arthrospira, formerly spirulina, a cyanobacteria in Lake Texcoco. They used tecuitlatl (cake made with spirulina) as a main dietary component. Most likely, the utilization of this cyanobacterium as food in Chad happened at the same period, or even earlier to the Kanem Empire (9th century) [9,12]. In a world with limited resources (energy, water and arable land, etc.) and intensifying anthropogenic pressure on the environment, the improvement of biotechnological processes to supply sustainable energy and renewable biomaterials from cleaner industrial processes constitutes a key challenge.

The genetic, phylogenetic and compositional nature of microalgal diversity is considerable, which makes them appealing for bioprospecting and the eventual industrial utilization of various biomolecules [13]. Nowadays, the principal industrial products from green microalgae are carotenoids and biomass for food, health and aquaculture [14]. These products are obtained from a restricted number of species; cyanobacterium from the Arthrospira genus constitutes 50% of world production, followed by green microalgae from the genera Chlorella, Dunaliella, Haematococcus, Nannochloropsis and the diatom Odontella [13]. Microalgae are usually selected based on both their growth properties and their aptitude to produce considerable amounts of specific metabolites. The efficiency of biomass production is a pivotal element of financial success in most of today’s commercial systems [14].

The production of such microalgal compounds depends on the variability of process and environmental conditions, which all have a direct effect on the value and quality of the target products. Quality control must therefore meet industry standards relating to toxicity and safety, the concentration of antioxidants and product characteristics relevant to marketability such as the taste and smell [14]. The market of microalgae applications remains in development, and the exploitation will spread into new areas. Given the huge microalgal diversity and modern technological progress of biotechnology, these microorganisms constitute so far major potential resources for novel products and applications [1]. Furthermore, as being broadly unexplored, the microalgae offer a major opportunity for discovery. The rediscovery rate (finding metabolites already described) should be superior to that of other groups of better-studied organisms.

During the current decades, the microalgal biotechnology acquired extensive and significant importance. Applications vary from biomass production for feeding to useful products for environmental applications [1]. Microalgal biotechnology is currently going through an unparalleled interest and investment worldwide [8]. For the last decade, researchers and industry developed various microalgal cultivation technologies that are in use today to produce biomass. Along with conventional fermentation reactors, two techniques are frequently applied in microalgae cultivation, specifically, outdoor and indoor production within photobioreactors. It is therefore important to develop and improve the diverse microalgae culture technologies to minimize production costs [11]. Growth rates significantly fluctuate between species and greatly depend on cultivation methods, especially the design of photobioreactors and the bioprocess conditions. In outdoor cultivation, extremophile species are preferred as they minimize the risk of contamination by competing organisms [14].

Recently, there has been a fast and significant progress in molecular engineering. As a result, the genetic technology applied to microalgae extended from the conventional process to systematic and synthetic regulation of metabolic pathways. Systems biology (including genomics, transcriptomics, proteomics and metabolomics) use two or more omics methods in order to define and to study a complex biological system. Synthetic biology aims to use standard biopartition as a basis for a new and fast biological implementation (e.g., transcriptome analysis combined to genome sequence might serve to predict promoter potency and operability). Metabolic engineering seeks to construct a strong host for the high production level of the chemical substance through genome editing and design of genetic circuits to redirect molecular flow of some metabolites [15].