Chater Keith F, Chandra Govind
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
J Microbiol. 2008 Feb;46(1):1-11. doi: 10.1007/s12275-007-0233-1.
In Streptomyces coelicolor, bldA encodes the only tRNA for a rare leucine codon, UUA. This tRNA is unnecessary for growth, but is required for some aspects of secondary metabolism and morphological development, as revealed by the phenotypes of bldA mutants in diverse streptomycetes. This article is a comprehensive review of out understanding of this unusual situation. Based on information from four sequenced genomes it now appears that, typically, about 2 approximately 3% of genes in any one streptomycete contain a TTA codon, most having been acquired through species-specific horizontal gene transfer. Among the few widely conserved TTA-containing genes, mutations in just one, the pleiotropic regulatory gene adpA, give an obvious phenotype: such mutants are defective in aerial growth and sporulation, but vary in the extent of their impairment in secondary metabolism in different streptomycetes. The TTA codon in adpA is largely responsible for the morphological phenotype of a bldA mutant of S. coelicolor. AdpA-dependent targets include several genes involved in the integrated action of extracellular proteases that, at least in some species, are involved in the conversion of primary biomass into spores. The effects of bldA mutations on secondary metabolism are mostly attributable to the presence of TTA codons in pathway-specific genes, particularly in transcriptional activator genes. This is not confined to S. coelicolor-it is true for about half of all known antibiotic biosynthetic gene sets from streptomycetes. Combined microarray and proteomic analysis of liquid (and therefore non-sporulating) S. coelicolor bldA mutant cultures revealed effects of the mutation during rapid growth, during transition phase, and in stationary phase. Some of these effects may be secondary consequences of changes in the pattern of ppGpp accumulation. It is argued that the preferential accumulation of the bldA tRNA under conditions in which growth is significantly constrained has evolved to favour the expression of genes that confer adaptive benefits in intermittently encountered sub-optimal environments. The evolution of this system may have been a secondary consequence of the selective pressure exerted by bacteriophage attack. Some biotechnological implications of bldA phenomenology are considered.
在天蓝色链霉菌中，bldA编码唯一用于稀有亮氨酸密码子UUA的tRNA。这种tRNA对生长并非必需，但对次级代谢和形态发育的某些方面却是必需的，这一点已通过不同链霉菌中bldA突变体的表型得到揭示。本文全面综述了我们对这种特殊情况的理解。基于来自四个已测序基因组的信息，现在看来，通常任何一种链霉菌中约2%至3%的基因含有TTA密码子，其中大多数是通过物种特异性水平基因转移获得的。在少数广泛保守的含TTA基因中，仅一个基因（多效调控基因adpA）发生突变就会产生明显的表型：此类突变体在气生菌丝生长和孢子形成方面存在缺陷，但在不同链霉菌中其次级代谢受损程度有所不同。adpA中的TTA密码子在很大程度上决定了天蓝色链霉菌bldA突变体的形态表型。AdpA依赖性靶点包括几个参与细胞外蛋白酶综合作用的基因，至少在某些物种中，这些蛋白酶参与将初级生物质转化为孢子的过程。bldA突变对次级代谢的影响主要归因于途径特异性基因中TTA密码子的存在，特别是在转录激活基因中。这并不局限于天蓝色链霉菌——对于链霉菌中约一半已知的抗生素生物合成基因集来说都是如此。对液体培养（因此不形成孢子）的天蓝色链霉菌bldA突变体培养物进行的微阵列和蛋白质组学联合分析揭示了该突变在快速生长阶段、过渡阶段和稳定期的影响。其中一些影响可能是ppGpp积累模式变化的次生后果。有人认为，在生长受到显著限制的条件下，bldA tRNA的优先积累已经进化，以利于在间歇性遇到的次优环境中赋予适应性益处的基因的表达。这个系统的进化可能是噬菌体攻击所施加的选择压力的次生结果。文中还考虑了bldA现象学的一些生物技术意义。
