Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.

The gene lmbB2 of the lincomycin biosynthetic gene cluster of Streptomyces lincolnensis ATCC 25466 was shown to code for an unusual tyrosine hydroxylating enzyme involved in the biosynthetic pathway of this clinically important antibiotic. LmbB2 was expressed in Escherichia coli, purified near to ho...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jitka Novotna, Jana Olsovska, Petr Novak, Peter Mojzes, Radka Chaloupkova, Zdenek Kamenik, Jaroslav Spizek, Eva Kutejova, Marketa Mareckova, Pavel Tichy, Jiri Damborsky, Jiri Janata
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/985c474f95164d1dbd6ad0c2af5718a4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:985c474f95164d1dbd6ad0c2af5718a4
record_format	dspace
spelling	oai:doaj.org-article:985c474f95164d1dbd6ad0c2af5718a42021-11-18T08:43:39ZLincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.1932-620310.1371/journal.pone.0079974https://doaj.org/article/985c474f95164d1dbd6ad0c2af5718a42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24324587/?tool=EBIhttps://doaj.org/toc/1932-6203The gene lmbB2 of the lincomycin biosynthetic gene cluster of Streptomyces lincolnensis ATCC 25466 was shown to code for an unusual tyrosine hydroxylating enzyme involved in the biosynthetic pathway of this clinically important antibiotic. LmbB2 was expressed in Escherichia coli, purified near to homogeneity and shown to convert tyrosine to 3,4-dihydroxyphenylalanine (DOPA). In contrast to the well-known tyrosine hydroxylases (EC 1.14.16.2) and tyrosinases (EC 1.14.18.1), LmbB2 was identified as a heme protein. Mass spectrometry and Soret band-excited Raman spectroscopy of LmbB2 showed that LmbB2 contains heme b as prosthetic group. The CO-reduced differential absorption spectra of LmbB2 showed that the coordination of Fe was different from that of cytochrome P450 enzymes. LmbB2 exhibits sequence similarity to Orf13 of the anthramycin biosynthetic gene cluster, which has recently been classified as a heme peroxidase. Tyrosine hydroxylating activity of LmbB2 yielding DOPA in the presence of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) was also observed. Reaction mechanism of this unique heme peroxidases family is discussed. Also, tyrosine hydroxylation was confirmed as the first step of the amino acid branch of the lincomycin biosynthesis.Jitka NovotnaJana OlsovskaPetr NovakPeter MojzesRadka ChaloupkovaZdenek KamenikJaroslav SpizekEva KutejovaMarketa MareckovaPavel TichyJiri DamborskyJiri JanataPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e79974 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jitka Novotna Jana Olsovska Petr Novak Peter Mojzes Radka Chaloupkova Zdenek Kamenik Jaroslav Spizek Eva Kutejova Marketa Mareckova Pavel Tichy Jiri Damborsky Jiri Janata Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.
description	The gene lmbB2 of the lincomycin biosynthetic gene cluster of Streptomyces lincolnensis ATCC 25466 was shown to code for an unusual tyrosine hydroxylating enzyme involved in the biosynthetic pathway of this clinically important antibiotic. LmbB2 was expressed in Escherichia coli, purified near to homogeneity and shown to convert tyrosine to 3,4-dihydroxyphenylalanine (DOPA). In contrast to the well-known tyrosine hydroxylases (EC 1.14.16.2) and tyrosinases (EC 1.14.18.1), LmbB2 was identified as a heme protein. Mass spectrometry and Soret band-excited Raman spectroscopy of LmbB2 showed that LmbB2 contains heme b as prosthetic group. The CO-reduced differential absorption spectra of LmbB2 showed that the coordination of Fe was different from that of cytochrome P450 enzymes. LmbB2 exhibits sequence similarity to Orf13 of the anthramycin biosynthetic gene cluster, which has recently been classified as a heme peroxidase. Tyrosine hydroxylating activity of LmbB2 yielding DOPA in the presence of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) was also observed. Reaction mechanism of this unique heme peroxidases family is discussed. Also, tyrosine hydroxylation was confirmed as the first step of the amino acid branch of the lincomycin biosynthesis.
format	article
author	Jitka Novotna Jana Olsovska Petr Novak Peter Mojzes Radka Chaloupkova Zdenek Kamenik Jaroslav Spizek Eva Kutejova Marketa Mareckova Pavel Tichy Jiri Damborsky Jiri Janata
author_facet	Jitka Novotna Jana Olsovska Petr Novak Peter Mojzes Radka Chaloupkova Zdenek Kamenik Jaroslav Spizek Eva Kutejova Marketa Mareckova Pavel Tichy Jiri Damborsky Jiri Janata
author_sort	Jitka Novotna
title	Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.
title_short	Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.
title_full	Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.
title_fullStr	Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.
title_full_unstemmed	Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.
title_sort	lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/985c474f95164d1dbd6ad0c2af5718a4
work_keys_str_mv	AT jitkanovotna lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT janaolsovska lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT petrnovak lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT petermojzes lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT radkachaloupkova lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT zdenekkamenik lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT jaroslavspizek lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT evakutejova lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT marketamareckova lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT paveltichy lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT jiridamborsky lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily AT jirijanata lincomycinbiosynthesisinvolvesatyrosinehydroxylatinghemeproteinofanunusualenzymefamily
_version_	1718421397603090432

Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family.

Ejemplares similares