High-Quality Draft Genome Sequence of the Actinobacterium Nocardia terpenica IFM 0406, Producer of the Immunosuppressant Brasilicardins, Using Illumina and PacBio Technologies

Buchmann, Anina; Eitel, Michael; Koch, Pierre; Schwarz, Paul N.; Stegmann, Evi; Wohlleben, Wolfgang; Wolański, Marcin; Krawiec, Michał; Zakrzewska‐Czerwińska, Jolanta; Méndez, Cármen; Botas, Alma; Núñez, Luz Elena; Morís, Francisco; Cortés, Jesús M.; Gross, Harald

doi:10.1128/genomea.01391-16

Cited by 14 publications

(14 citation statements)

References 20 publications

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“…The GenBank accession number of the genome sequence, of N. terpenica IFM0406 is LWGR00000000.1 [41] , GenBank accession number of A. japonicum is CP008953 [42] .…”

Section: Methodsmentioning

confidence: 99%

Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production

Schwarz

Roller

Kulik

et al. 2018

Synthetic and Systems Biotechnology

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The isoprenoid brasilicardin A is a promising immunosuppressant compound with a unique mode of action, high potency and reduced toxicity compared to today's standard drugs. However, production of brasilicardin has been hampered since the producer strain Nocardia terpenica IFM0406 synthesizes brasilicardin in only low amounts and is a biosafety level 2 organism. Previously, we were able to heterologously express the brasilicardin gene cluster in the nocardioform actinomycete Amycolatopsis japonicum. Four brasilicardin congeners, intermediates of the BraA biosynthesis, were produced. Since chemical synthesis of the brasilicardin core structure has remained elusive we intended to produce high amounts of the brasilicardin backbone for semi synthesis and derivatization. Therefore, we used a metabolic engineering approach to increase heterologous production of brasilicardin in A. japonicum. Simultaneous heterologous expression of genes encoding the MVA pathway and expression of diterpenoid specific prenyltransferases were used to increase the provision of the isoprenoid precursor isopentenyl diphosphate (IPP) and to channel the precursor into the direction of diterpenoid biosynthesis. Both approaches contributed to an elevated heterologous production of the brasilicardin backbone, which can now be used as a starting point for semi synthesis of new brasilicardin congeners with better properties.

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“…The GenBank accession number of the genome sequence, of N. terpenica IFM0406 is LWGR00000000.1 [41] , GenBank accession number of A. japonicum is CP008953 [42] .…”

Section: Methodsmentioning

confidence: 99%

Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production

Schwarz

Roller

Kulik

et al. 2018

Synthetic and Systems Biotechnology

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show abstract

“…The GenBank accession number of the genome sequence, of N. terpenica IFM 0406 is LWGR00000000.1, of A. japonicum is CP008953 …”

Section: Methodsmentioning

confidence: 99%

“…The pathogenic actinobacteria Nocardia terpenica IFM 0406 (formerly referred to as Nocardia brasiliensis IFM 0406) was described to produce the immunosuppressant brasilicardin A (BraA) …”

Section: Introductionmentioning

confidence: 99%

The Immunosuppressant Brasilicardin: Determination of the Biosynthetic Gene Cluster in the Heterologous Host Amycolatopsis japonicum

Schwarz

Buchmann

Roller

et al. 2017

Biotechnology Journal

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Nocardia terpenica IFM 0406 is the producer of the immunosuppressants brasilicardins A-D. Brasilicardin is a promising compound because of its unique mode of action and its higher potency and reduced toxicity compared to today's standard drugs. However, production of brasilicardin is so far hampered as Nocardia terpenica IFM 0406 synthesizes brasilicardin in only low amounts and represents a human pathogen (biosafety level 2 BSL2). In order to achieve a safe and high yield production of brasilicardin A (BraA), the authors heterologously express the brasilicardin gene cluster in the nocardioform actinomycete Amycolatopsis japonicum (A. japonicum::bcaAB01), which is fast growing, genetically accessible and closely related to N. terpenica IFM 0406. In A. japonicum::bcaAB01, four brasilicardin congeners, intermediates of the BraA biosynthesis, are produced. Investigation of the genes flanking the previously defined brasilicardin biosynthetic gene cluster revealed two novel genes (bra0, bra12), which are involved in brasilicardin biosynthesis: bra12 encodes a transcriptional activator of the brasilicardin gene cluster. bra0 codes for a dioxygenase involved in methoxylation of brasilicardin. Based on this finding the authors are able to revise the proposed brasilicardin biosynthesis.

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“…Within the course of our genome-driven investigations of Nocardia strains ( 4 – 6 ), we noted that a genome sequence of IFM 0706 T was available under its synonymous designation N. terpenica NBRC 100888 T (GenBank accession number BAGI00000000.1 ). However, an annotation was missing, and the genome is highly fragmented.…”

Section: Announcementmentioning

confidence: 99%

“…However, an annotation was missing, and the genome is highly fragmented. In addition, in comparison with closely related strains ( 4 , 7 ), we hypothesized that the genome size of 8.63 Mbp might be too small. In order to close the significant genomic gaps and to increase the genomic resolution focused on secondary metabolism, we resequenced the genome of strain IFM 0706 T .…”

Section: Announcementmentioning

confidence: 99%

Improved De Novo Draft Genome Sequence of the Nocavionin-Producing Type Strain Nocardia terpenica IFM 0706 and Comparative Genomics with the Closely Related Strain Nocardia terpenica IFM 0406

Buchmann

Gross

2020

Microbiol Resour Announc

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High-Quality Draft Genome Sequence of the Actinobacterium Nocardia terpenica IFM 0406, Producer of the Immunosuppressant Brasilicardins, Using Illumina and PacBio Technologies

Cited by 14 publications

References 20 publications

Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production

Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production

The Immunosuppressant Brasilicardin: Determination of the Biosynthetic Gene Cluster in the Heterologous Host Amycolatopsis japonicum

Improved De Novo Draft Genome Sequence of the Nocavionin-Producing Type Strain Nocardia terpenica IFM 0706 and Comparative Genomics with the Closely Related Strain Nocardia terpenica IFM 0406

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