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Reprogramming Microbial Metabolic Pathways pp 115–138Cite as

Cascades and Networks of Regulatory Genes That Control Antibiotic Biosynthesis

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 64))

Abstract

Onset of the biosynthesis of bioactive secondary metabolites in batch cultures of actinomycetes occurs after the rapid growth phase, following a transition phase which involves complex metabolic changes. This transition is triggered by nutrient starvation or by other environmental stress signals. Expression of genes encoding bioactive secondary metabolites is governed by cascades of pathway specific regulators and networks of cross-talking global regulators. Pathway specific regulators such as Streptomyces antibiotic regulatory proteins, LAL-type and LysR-type regulators respond to autoregulatory proteins that act in concert with their cognate ligands (e.g. γ-butyrolactone receptor proteins and their cognate γ-butyrolactone ligands). Global regulators such as PhoR-PhoP and other two component systems and orphan response regulators, such as GlnR, control set of genes affecting primary and secondary metabolism. GlnR and, therefore, nitrogen metabolism genes are under phosphate control exerted by binding of PhoP to PHO boxes located in the promoter region of GlnR. A few pleiotropic regulatory genes, such as areB (ndgR), dmdR1 or dasR connect primary metabolism (amino acid biosynthesis, N-acetylglucosamine or iron levels) with antibiotic biosynthesis. Some atypical response regulators that require specific small ligands appear to be involved in feedback control of antibiotic production. All these mechanisms together modulate, in a coordinated manner, different aspects of Streptomyces metabolism as a real “protection net” that prevents drastic changes in metabolism that may be deleterious for cell survival.

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Abbreviations

ARE:

autoregulatory element

ARR:

atypical response regulators

BRP:

butyrolactone receptor protein

CDA:

calcium-dependent antibiotic

EMSA:

electrophoretic mobility shift assay

GlcNac:

N-acetyl-glucosamine

HTH:

helix-turn-helix

i-TRAQ:

isobaric tags for relative and absolute quantification

LAL:

large ATP-binding regulators of the LuxR family

LC-MS/MS:

liquid chromatography mass spectrometry

PHO box:

sequence for PhoP binding

Q-RT-PCR:

quantitative reverse polymerase chain reaction

SARP:

Streptomyces antibiotic regulatory protein

TCS:

two component systems

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Acknowledgements

This article was supported by Grants BIO2009-09820 to P. Liras and BIO2010-16094 to Juan F. Martín, of the CICYT, Spanish Ministry of Economy and Competitivity, and by the European ERA-IB2 Project PIM2010EE1-00677 “INMUNOTEC” to both authors.

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  1. Department of Molecular Biology, University of León, León, 24071, Spain

    Juan F. Martín & Paloma Liras

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  1. Juan F. Martín
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Correspondence to Juan F. Martín .

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  1. , State Key Laboratory, Jiangnan University, Lihu Avenue 1800, Wuxi, 214122, Jiangsu, China, People's Republic

    Xiaoyuan Wang

  2. School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, 214122, China, People's Republic

    Jian Chen

  3. , Div. of Life Sciences, King's College London, Stamford Street 150, London, SE1 9NH, United Kingdom

    Peter Quinn

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Martín, J.F., Liras, P. (2012). Cascades and Networks of Regulatory Genes That Control Antibiotic Biosynthesis. In: Wang, X., Chen, J., Quinn, P. (eds) Reprogramming Microbial Metabolic Pathways. Subcellular Biochemistry, vol 64. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5055-5_6

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