Genetic Engineering in Combination with Semi-Synthesis Leads to a New Route for Gram-Scale Production of the Immunosuppressive Natural Product Brasilicardin A.

Brasilicardin A (1) consists of an unusual anti/syn/anti-perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre-clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low-yielding fermentation process using a pathogenic organism and an elaborate, multi-step total synthesis.

A novel LysR-type regulator negatively affects biosynthesis of the immunosuppressant brasilicardin.

Brasilicardin A (BraA) is a promising immunosuppressive compound produced naturally by the pathogenic bacterium IFM 0406. Heterologous host expression of brasilicardin gene cluster showed to be efficient to bypass the safety issues, low production levels and lack of genetic tools related with the use of native producer. Further improvement of production yields requires better understanding of gene expression regulation within the BraA biosynthetic gene cluster (Bra-BGC); however, the only so far known regulator of this gene cluster is Bra12.

Improved 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.

We report an improved draft genome sequence of the human-pathogenic strain IFM 0706 The resequencing unveiled that the genome size is larger than anticipated, reducing significantly the number of contigs and building a basis for comparison with the closely related strain IFM 0406.

Draft Genome Sequence of sp. Strain MC-1LL, a Bacterial Strain with Antimicrobial Properties, Isolated from Marine Sediments in Nigeria.

Here, we report a 4.3-Mb draft genome sequence of a potential new species, which clarified its taxonomic position and gave insight into the complete secondary metabolite production capacity of the strain.

Continuous Adaptive Evolution of a Fast-Growing Strain Independent of Protocatechuate.

is a commonly applied host for the industrial production of amino acids. While valued for its robustness, it is somewhat inferior to competing strains such as because of the relatively low growth rate of 0.40 h in synthetic, industrial media.

Draft Genome Sequence of the Novonestmycin-Producing Strain Streptomyces sp. Z26, Isolated from Potato Rhizosphere in Morocco.

Streptomyces sp. strain Z26 exhibited antifungal activity and turned out to be a producer of the secondary metabolites novonestmycin A and B. The 6.

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

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).

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

The bacterium Nocardia terpenica IFM 0406 is known as the producer of the immunosuppressant brasilicardin A. Here, we report the completely sequenced genome of strain IFM 0406, which facilitates the heterologous expression of the brasilicardin biosynthetic gene cluster but also unveils the intriguing biosynthetic capacity of the strain to produce secondary metabolites.