Abstract
Streptomycetes have huge linear genomes (>8 Mbp), extreme GC content (around 70 mol%), and their life cycles involve vegetative growth, a phase with formation of aerial hyphae and a sporulation stage. In addition, they produce a range of secondary metabolites, including many of the antibiotics used in clinics today, and for this reason they have immense practical importance. Production of antibiotics is typically closely linked to differentiation. One of the key genes involved in the differentiation switch is bldA, which encodes the tRNA recognizing the very rare UUA (leucine) codons (Lawlor et al., 1987). It has been shown that the production of this tRNA is subject to temporal regulation as it becomes abundant in old cultures (Leskiw et al., 1993). Conversely, genes containing UUA codons are often linked to antibiotic production or other aspects of differentiation (see reviews by Leskiw et al., 1991a; Chater, 1993). As a consequence, heterologous expression of proteins, which often takes place in liquid cultures under vegetative growth, can be problematic if the foreign gene contains UUA codons (Leskiw et al., 1991b; Ueda et al., 1993). Codon usage in the streptomycetes is therefore an interesting phenomenon that deserves full attention.