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Chapter 11 : Regulation of Antibiotic Biosynthesis in Producer Organisms

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Regulation of Antibiotic Biosynthesis in Producer Organisms, Page 1 of 2

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Abstract:

Of the circa 12,000 known antibiotics, it has been estimated that some 160 are or have been in human clinical use. Streptomycetes, gram-positive filamentous bacteria, account for these production of about 55% of the commercially significant antibiotics. The Abs knockout leads to precocious production of all the antibiotics in hours to days and in amounts up to 60-fold higher than normal, dependent on the culture conditions. The most extensive analysis of regulation of a specific antibiotic pathway, one step down from the Abs global regulators, is probably in in production of the two antibiotics virginiamycin M1 and virginiamycin S1. The hydrophobic side chain of the butyrolactones, known generically also as butaneolides, is in the same locus as the N-acyl moiety of the gram-negative quorum molecules. A schematic for regulation of biosynthetic gene expression for the major classes of streptomycete antibiotics (polyketides, nonribosomal peptides, and aminoglycosides) is beginning to take shape. Plant pathogenic bacteria often secrete enzymes (exoenzymes) with hydrolytic capacity to destroy the components of plant cell walls to release the nutrients that can then be utilized by the pathogens. The N-acylhomoserine lactones of , , and many other bacteria and the γ-butyrolactones of streptomycetes, serve equivalent purposes, as low-molecular-weight pheromones, for communicating population density-dependent signals between bacteria of the same species.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11

Key Concept Ranking

Gene Expression and Regulation
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Gram-Positive Filamentous Bacteria
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Plant Pathogenic Bacteria
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Figures

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Untitled

, the vancomycin producer, and , the producer of calcium-dependent antibiotic.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.1
Figure 11.1

(A) (from Miyadoh et al. [1997], with permission); (B) (from www.cbs.umn.edu/asirc, © 1997, with permission); (C) ; (D)

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.2
Figure 11.2

Structures of secondary metabolites produced by .

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.3
Figure 11.3

Two-component regulatory logic for antibiotic gene transcriptional control by Abs1 and Abs2 in streptomycetes.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.4
Figure 11.4

Structures of virginiamycin antibiotics.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Figure 11.5

Comparison of quorum-sensing molecules.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.6
Figure 11.6

Different redox states at C of butaneolide quorum-signaling molecules and differential interaction with streptomycete transcriptional repressors ArpA, FarA, and BarA.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Figure 11.7

Proposed biosynthetic pathway for the quorum-sensing butaneolides.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Figure 11.8

(A) SARP are homologs of OmpR; (B) structure of the OmpR transcription factor.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.9
Figure 11.9

Butaneolide and virginiamycin S in coordinate regulation of virginiamycin biosynthesis.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.10
Figure 11.10

Schematic for signal input and regulatory networks controlling antibiotic production in streptomycetes. (From Bibb [1996], with permission.)

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.11
Figure 11.11

Regulation of exoenzyme and carbapenem antibiotic production in by the acylhomoserine lactone OHHL.

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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Image of Figure 11.12
Figure 11.12

A double cascade of quorum-signaling -acylhomoserine lactones in

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11
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References

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Tables

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Table 11.1

Selected actinomycete antibiotics

Citation: Walsh C. 2003. Regulation of Antibiotic Biosynthesis in Producer Organisms, p 159-173. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch11

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