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Chapter 1 : Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges

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Abstract:

Much of the genetic and physiological experimentation on developmental regulation focuses on the two streptomycete species and because they are relatively tractable as experimental organisms, but the diversity in morphological forms and bioactive compounds found among streptomycetes and their relatives in the genus is enormous. The actinomycetes produce an enormous variety of bioactive molecules. The enzyme activity responsible for doxorubicin chain synthesis, classified as a polyketide synthase, is evolutionarily related to bacterial fatty acid synthases. Two significant observations have suggested that temporal regulation of -ORF4 transcription is largely responsible for growth phase-dependent antibiotic production in defined media. First, accumulation of the -ORF4 transcript is limited to the postexponential growth period. Second, introduction of extra plasmid-borne copies of -ORF4 causes exponential-phase actinorhodin production. Disruption mutations in certain other genes identified for a physiological attribute also produce a Bld phenotype, indicating that Bld mutant hunts have not saturated the phenotype. The examples discussed in this chapter include mutations generated in and . The genetic elements responsible for global regulation are now being discovered through a variety of experimental approaches, primarily utilizing and the closely related . Among the numerous complex nutritional, physiological, and environmental effects on antibiotic synthesis and morphogenesis that have been documented, the carbon metabolism, cyclic AMP (cAMP), GTP levels, ppGpp phenomena have been genetically analyzed. Some streptomycetes have a tendency to genetic instability, particularly affecting morphogenesis and antibiotic production.

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 1

Phylogenetic relationships among actinomycetes, based on 16S ribosomal DNA and rRNA sequence comparisons. The 10 suborders of the order are shown, but only representative families and genera (more than 100 genera are classified). Also, the class contains several other minor suborders. The scale bar represents approximately five nucleotide substitutions per 100 nucleotides among the families of the order ( ). The hatched bar indicates the presence of a shared insertion in the 23S rRNA. Groups marked with asterisks are represented in Fig. 2 to 10 . (Based on and .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 2

SF 2425. (Provided by S. Amano, S. Miyadoh, and T. Shomura. Reprinted with permission from )

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 3

sp. strain Brunchorst 1886. (Provided by D. O. Baker and H. A. Lechevalier. Reprinted with permission from )

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 4

Dermatophilus congolensis. Bar, 10 (Jim. (Provided by A. Masters andj. M. Carson. Reprinted with permission from .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 5

. Bar, 1.0 |JLm. (Provided by K. Ochiai, S. Kinoshita, and K. Ando. Reprinted with permission from .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 6

. Bar, 1.0 µm. (Provided by T. Tamura, T. Nishii, and K. Hatano. Reprinted with permission from .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 7

. Bar, 5 µm. (Provided by S. Amano, J. Yoshida, and T. Shomura. Reprinted with permission from .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 8

sp. Left, spore; right, sporangium. (Provided by S. Amano and S. Miyadoh, and H. Suzuki and A. Seino, respectively. Reprinted with permission from .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 9

Micromonospora sp. strain SF2259. Bar, 1.0 µm. (Provided by S. Amano, J. Yoshida, and T. Shomura. Reprinted with permission from .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 10

SK 2457. Bar, 1.0 µn. (Provided by S. Miyadoh, S. Amano, and T. Shomura. Reprinted with permission from .)

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 11

Elements of the doxorubicin-daunorubicin gene cluster ( ). Doxorubicin is an anthracycline product of a mutant S. peucetius; the parent makes the closely related compound daunorubicin. The pointed bars indicate ORFs; those with single letters are genes, , , and indicate various biosynthetic genes; the polyketide synthase includes the solid gene symbols. Gray shading indicates regulatory genes, which are , -O, and -I ( regulates expression of ), and indicates resistance genes. The genes all lie in a single large cluster, which is broken into two lines in the illustration. CoA, coenzyme A.

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 12

Elements of the related streptomycin and 5′-hydroxy-streptomy-cin gene clusters of the producing organisms ( ). The pointed bars indicate transcription units, and indicate the various biosynthetic genes. is the streptomycin-specific regulator. encodes streptomycin phosphotransferase, a resistance enzyme. Heavy diagonal hatching indicates conserved gene organization. Vertical hatching and light-gray shading indicate partially conserved and inverted gene orders, respectively. P indicates promoter regions. Light diagonal hatching indicates defined binding sites for StrR.

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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FIGURE 13

(A) A-factor () contains a 6-keto group, IM-2 ( sp. strain FR.I-5) contains a 6-β-hydroxy group, and virginiae butanolides (the VB group of ) contain a 6-α-hydroxy group. The autoinducer of luminescence (AHL) is also shown. (B) A-factor regulation of aerial-mycelium formation, streptomycin production, and streptomycin resistance in . ArpA regulates AdpA, which regulates the streptomycin-specific activator, StrR. StrR translation requires the -encoded tRNA. StrR binds promoter regions shown as shaded boxes, and so regulates biosynthetic genes and , the streptomycin phosphotransferase gene. Only part of the streptomycin gene cluster is shown. A-factor also requires the -encoded tRNA for translation. AmfR is a response regulator; its cognate kinase is not known, nor are its targets. Orf4 and Orf5 functions are unknown.

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1
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References

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Tables

Generic image for table
TABLE 1

Natural actinomycete bioactive products

Citation: Champness W. 2000. Actinomycete Development, Antibiotic Production, and Phylogeny: Questions and Challenges, p 11-31. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch1

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