Cyanobacteria and algae are becoming increasingly attractive cell factories for producing renewable biofuels and chemicals due to their ability to capture solar energy and CO₂ and their relatively simple genetic background for genetic manipulation. Increasing research efforts from the synthetic biology approach have been made in recent years to modify cyanobacteria and algae for various biotechnological applications. In this article, we critically review recent progresses in developing genetic tools for characterizing or manipulating cyanobacteria and algae, the applications of genetically modified strains for synthesizing renewable products such as biofuels and chemicals. In addition, the emergent challenges in the development and application of synthetic biology for cyanobacteria and algae are also discussed.

Recent studies have revealed the prevalence and biological significance of guanidine metabolism in nature. However, the metabolic pathways used by microbes to degrade guanidine or mitigate its toxicity have not been widely studied. Here, via comparative proteomics and subsequent experimental validation, we demonstrate that Sll1077, previously annotated as an agmatinase enzyme in the model cyanobacterium Synechocystis sp. PCC 6803, is more likely a guanidinase as it can break down guanidine rather than agmatine into urea and ammonium. The model cyanobacterium Synechococcus elongatus PCC 7942 strain engineered to express the bacterial ethylene-forming enzyme (EFE) exhibits unstable ethylene production due to toxicity and genomic instability induced by accumulation of the EFE-byproduct guanidine. Co-expression of EFE and Sll1077 significantly enhances genomic stability and enables the resulting strain to achieve sustained high-level ethylene production. These findings expand our knowledge of natural guanidine degradation pathways and demonstrate their biotechnological application to support ethylene bioproduction.

Escalating concerns about CO₂ emission from fossil fuel utilization and environmental pollution from fossil-derived plastic waste call for the sustainable production and utilization of renewable biodegradable plastic materials. Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible thermoplastics with thermal and mechanical properties comparable to conventional plastics; thus, they are promising materials to mitigate environmental pollution. (R)-3-Hydroxybutyrate (3HB), which is the most common building-block for PHAs, has the potential to be utilized in various medical applications and can also serve as a precursor to a variety of value-added stereospecific chemicals. In addition, it can be produced by microorganisms, such as engineered cyanobacteria, from inexpensive renewable resources such as waste CO₂. However, higher titer and rate of (R)-3HB production by cyanobacteria beyond that found in the current literature are critical for commercial applications. Herein, we employed a facile strategy to identify the rate-limiting step in the photoautotrophic production of (R)-3HB by the cyanobacterium Synechocystis and found that acetoacetyl-CoA reductase activity is the bottleneck in the process. Optimization of the gene's ribosome binding site led to a 2.2-fold increase in enzyme activity. In the culture medium of the engineered organism, the (R)-3HB titer reached 1.84 g L⁻¹ within 10 days, with a peak productivity of 263 mg L⁻¹ day⁻¹, using CO₂ and light as the sole carbon and energy sources. Moreover, dramatic changes in carbon partition were discovered in the (R)-3HB-producing cells along the course of cultivation using ¹³C-metabolic flux analysis; after the rapid growth phase, a majority of carbon flux was redirected from the cell mass formation to the production of (R)-3HB in the engineered Synechocystis under the examined experimental conditions.