In contrast to conventional recombinant DNA techniques, synthetic DNA synthesis can generate nucleotide sequences de novo. In this way, DNA synthesis technology allows for custom design of novel nucleotide sequences. The increased throughput of DNA synthesis now allows entire genetic regions and even small genomes to be derived synthetically (Carr and Church 2009; Gibson et al. 2008). This break­through has given rise to the field of ‘synthetic genomics’. DNA synthesis tech­niques hold promising applications in algae biofuel research.

DNA synthesis, coupled with recombinant techniques, can generate over 1 Mb of synthetically derived nucleotide sequence. DNA synthesis technology alone can produce customized sequences of up to 10 kb (known as a cassette) (Gibson et al. 2010a). Assembly of multiple cassettes using in vitro recombination techniques can create large synthetic DNA constructs (up to 150 kb). Larger constructs (>500 kb) can be achieved when in vivo recombination techniques are used (Gibson et al.

2008) . Synthesizing small genomes synthetically is now possible. Bacteriophage and viral genomes (5-8 kb) can be created by synthetic oligonucleotides alone (Cello et al. 2002; Liu et al. 2012; Smith et al. 2003). Mitochondrial and chloroplast genomes have also been synthesized and assembled (16 and 242 kb respectively) (Gibson et al. 2010b; O’Neill et al. 2012). The Mycoplasma mycoides bacterial genome (1.08 Mb) is currently the largest published assembly. Importantly, the M. mycoides synthetic genome was shown to be biologically viable. This synthetic genome was able to ‘boot-up’ and co-ordinate normal cell function when it replaced genomic DNA of a M. capricolum recipient cell (Gibson et al. 2010a).

Genome synthesis promises unrestricted editing of whole genome sequence. Presently, small autonomous or semi autonomous genetic circuits have been introduced into cells to perform a desired role (Havens et al. 2012; Tigges et al.

2009) . Synthetic genomics strives to widen the scale and complexity of circuitry, ultimately delivering new novel phenotypes. Crucially, synthetic genomics must be partnered with CAD tools (such as SynBioSS) to ensure ease of hypothesis testing in silico before embarking on lengthy wet-lab experiments.

Synthetic genomics also enables global editing of cis-regulatory elements. This approach was recently trialed in a biologically active synthetic yeast chromosome. No gross changes to gene circuitry were attempted; rather 98 small elements (loxPsym sites) were introduced throughout the chromosome. When ectopically activated, these sites could initiate chromosomal deletion events (Annaluru et al.

2014) . This demonstrated that incorporating small sequence additions by synthetic DNA synthesis can provide unprecedented control of chromosome architecture.

Synthetic genomics is still in its infancy. Technical problems of synthetic assembly exist. The error rate of DNA synthesis, even at 1 x 10-5 bp, is still problematic when synthesizing large nucleotide stretches (Carr et al. 2004). Such base misincorporations have shown to render entire genomic assemblies biologi­cally inactive (Katsnelson 2010). Stability of constructs in host cells during in vivo recombination (e. g. E. coli or Saccharomyces cerevisiae) significantly limits assembly size. The Prochlorococcus marinus genome assembly (1.7 Mb) is cur­rently the largest stably maintained synthetic construct (however it has not been proven biologically active) (Tagwerker et al. 2012). Furthermore small synthetic genomes that have shown to be biologically active were replicates of known genomes. DNA synthesis may support the introduction of novel genetic regions, however building functional gene circuits from the bottom up has been shown problematic (Katsnelson 2010).