Effects of deletions of mbtH-like genes on clorobiocin biosynthesis in Streptomyces coelicolor

Wolpert, Manuel; Gust, Bertolt; Kammerer, Bernd; Heide, Lutz

doi:10.1099/mic.0.2006/002998-0

Cited by 66 publications

(67 citation statements)

References 55 publications

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“…Our previous in vivo studies showed that cdaX can functionally replace cloY in the biosynthesis of the aminocoumarin moiety of clorobiocin (2).…”

Section: Expression and Purification Of Tyrosine-adenylating Enzymes mentioning

confidence: 99%

“…enterobactin and mycobactin), and other bioactive molecules (1). The activated amino acids can be assembled to peptides by non-ribosomal peptide synthases (NRPSs), 2 leading, for example, to the backbone of vancomycin or can serve as precursors of non-peptidic antibiotics such as novobiocin, clorobiocin, and simocyclinone D8 (Fig. 1).…”

mentioning

confidence: 99%

“…The function of mbtH-like genes has remained enigmatic for many years. The first proof that these genes are essential for secondary metabolite production was provided by a gene inactivation and complementation study by our group in clorobiocin biosynthesis (2) and by a similar study in the biosynthesis of coelichelin and calcium-dependent antibiotics (3). In vivo investigations were complicated by the fact that many bacterial genomes contain several mbtHlike genes that can functionally replace each other.…”

mentioning

confidence: 99%

“…In vivo investigations were complicated by the fact that many bacterial genomes contain several mbtHlike genes that can functionally replace each other. The importance of a specific mbtH-like gene for the biosynthesis of a secondary metabolite can be assessed only after all other mbtHlike genes in the genome have been inactivated (2,3). However, in vivo studies could not define the precise physiological function of the mbtH-like genes, e.g.…”

mentioning

confidence: 99%

“…2B). In vivo studies have suggested that the formation of the aminocoumarin moiety of clorobiocin requires an intact mbtH-like gene, but the identical reaction sequence in novobiocin biosynthesis does not (2). Given the facts that the tyrosine-adenylating enzyme NovH has the same size (600 amino acids) as CloH and that both proteins share 83% identity in their amino acid sequences (supplemental Fig.…”

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confidence: 99%

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Role of MbtH-like Proteins in the Adenylation of Tyrosine during Aminocoumarin and Vancomycin Biosynthesis

Boll

Taubitz

Heide

2011

Journal of Biological Chemistry

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109

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Background: L-Tyrosine adenylation is a key step in aminocoumarin antibiotic and vancomycin biosynthesis. Results: Several but not all tyrosine-adenylating enzymes require MbtH-like proteins for activity, forming heterotetrameric complexes. A single Leu-to-Met mutation creates an MbtH-independent enzyme. Conclusion and Significance: MbtH-like proteins are essential tools in the combinatorial biosynthesis of antibiotics.

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“…Our previous in vivo studies showed that cdaX can functionally replace cloY in the biosynthesis of the aminocoumarin moiety of clorobiocin (2).…”

Section: Expression and Purification Of Tyrosine-adenylating Enzymes mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Role of MbtH-like Proteins in the Adenylation of Tyrosine during Aminocoumarin and Vancomycin Biosynthesis

Boll

Taubitz

Heide

2011

Journal of Biological Chemistry

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109

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Nicht‐ribosomale Peptidsynthese – Prinzipien und Perspektiven

Süßmuth

Mainz

2017

Angewandte Chemie

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Nicht‐ribosomale Peptidsynthetasen (NRPSs) sind große Multienzymmaschinerien, die zahlreiche Peptide mit enormer struktureller und funktionaler Diversität erzeugen. Unter diesen Produkten befinden sich mehr als 20 auf dem Markt befindliche Wirkstoffe, darunter Antibiotika (Penicillin, Vancomycin), antitumorale Medikamente (Bleomycin) und Immunsuppressiva (Cyclosporin). In den vergangenen Jahrzehnten haben biochemische sowie strukturbiologische Studien mechanistische Einblicke in die hochkomplexen NRPSs gewährt. Dieser Aufsatz fasst den aktuellen Kenntnisstand über die zugrundeliegenden Mechanismen von NRPSs zusammen und gibt einen Überblick über die Vielfalt ihrer Produkte. Ebenso behandelt werden die Probleme und Herausforderungen, die mit der Umprogrammierung von NRPS‐Systemen einhergehen. Das Potenzial einer solchen Umprogrammierung liegt begründet in einer nachhaltigen Generierung von Wirkstoffanaloga und neuen Substanzbibliotheken, die anderenfalls kaum zugänglich sind.

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Nonribosomal Peptide Synthesis—Principles and Prospects

2017

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Nonribosomal peptide synthetases (NRPSs) are large multienzyme machineries that assemble numerous peptides with large structural and functional diversity. These peptides include more than 20 marketed drugs, such as antibacterials (penicillin, vancomycin), antitumor compounds (bleomycin), and immunosuppressants (cyclosporine). Over the past few decades biochemical and structural biology studies have gained mechanistic insights into the highly complex assembly line of nonribosomal peptides. This Review provides state-of-the-art knowledge on the underlying mechanisms of NRPSs and the variety of their products along with detailed analysis of the challenges for future reprogrammed biosynthesis. Such a reprogramming of NRPSs would immediately spur chances to generate analogues of existing drugs or new compound libraries of otherwise nearly inaccessible compound structures.

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Effects of deletions of mbtH-like genes on clorobiocin biosynthesis in Streptomyces coelicolor

Cited by 66 publications

References 55 publications

Role of MbtH-like Proteins in the Adenylation of Tyrosine during Aminocoumarin and Vancomycin Biosynthesis

Role of MbtH-like Proteins in the Adenylation of Tyrosine during Aminocoumarin and Vancomycin Biosynthesis

Nicht‐ribosomale Peptidsynthese – Prinzipien und Perspektiven

Nonribosomal Peptide Synthesis—Principles and Prospects

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