Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds
The biosynthetic gene clusters (BGCs) for the macrocyclic lactone-based polyketide compounds are extremely large-sized because the polyketide synthases that generate the polyketide chains of the basic backbone are of very high molecular weight. In developing a heterologous expression system for the...
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| Veröffentlicht in: | Journal of antibiotics 2024-05, Vol.77 (5), p.288-298 |
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| creator | Kudo, Kei Nishimura, Takehiro Izumikawa, Miho Kozone, Ikuko Hashimoto, Junko Fujie, Manabu Suenaga, Hikaru Ikeda, Haruo Satoh, Nori Shin-ya, Kazuo |
| description | The biosynthetic gene clusters (BGCs) for the macrocyclic lactone-based polyketide compounds are extremely large-sized because the polyketide synthases that generate the polyketide chains of the basic backbone are of very high molecular weight. In developing a heterologous expression system for the large BGCs amenable to the production of such natural products, we selected concanamycin as an appropriate target. We obtained a bacterial artificial chromosome (BAC) clone with a 211-kb insert harboring the entire BGC responsible for the biosynthesis of concanamycin. Heterologous expression of this clone in a host strain,
Streptomyces avermitilis
SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as
ent
-gephyromycin and a novel compound that was designated JBIR-157. We describe herein sequencing and expression studies performed on these BGCs, demonstrating the utility of large BAC clones for the heterologous expression of cryptic or near-silent loci. |
| doi_str_mv | 10.1038/s41429-024-00711-9 |
| format | Article |
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Streptomyces avermitilis
SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as
ent
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Streptomyces avermitilis
SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as
ent
-gephyromycin and a novel compound that was designated JBIR-157. We describe herein sequencing and expression studies performed on these BGCs, demonstrating the utility of large BAC clones for the heterologous expression of cryptic or near-silent loci.</description><subject>42/40</subject><subject>42/44</subject><subject>45/23</subject><subject>631/326/22/1290</subject><subject>631/326/41/2173</subject><subject>631/92/349</subject><subject>631/92/60</subject><subject>Antibiotics</subject><subject>Artificial chromosomes</subject><subject>Bacterial artificial chromosomes</subject><subject>Bacteriology</subject><subject>Biological Products - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Bioorganic Chemistry</subject><subject>Biosynthesis</subject><subject>Chromosomes, Artificial, Bacterial - genetics</subject><subject>Cloning</subject><subject>Cloning, Molecular</subject><subject>Gene clusters</subject><subject>Genes</subject><subject>Genomes</subject><subject>Life Sciences</subject><subject>Medicinal Chemistry</subject><subject>Metabolites</subject><subject>Microbiology</subject><subject>Microorganisms</subject><subject>Molecular weight</subject><subject>Multigene Family</subject><subject>Natural products</subject><subject>Organic Chemistry</subject><subject>Polyketide Synthases - genetics</subject><subject>Polyketide Synthases - metabolism</subject><subject>Polyketides</subject><subject>Polyketides - metabolism</subject><subject>Streptomyces - genetics</subject><subject>Streptomyces - metabolism</subject><issn>0021-8820</issn><issn>1881-1469</issn><issn>1881-1469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1q3DAUhUVpaSZpX6CLIuimG7f680hahiFpAoFu2rWQZXlGQbZcSS7MY-SNe91JGugiIJDQ_e65RzoIfaDkCyVcfS2CCqYbwkRDiKS00a_QhipFGyq2-jXaEMJooxQjZ-i8lHtCuORSvUVnXAlYWm_Qw87Otgsx1CNOA7Y42rz3uLOu-hxsxDbXMAS3Ht0hpzGVNHrsYpo8PtjcpRymPR6XWMMcoTGkcpzqwdfg8N5PK7oU0Cp4SBlDAc859YurIU3rxD78hiJgaZzTMvXlHXoz2Fj8-8f9Av28vvqxu2nuvn-73V3eNU6otjaaE23haULpTgrKCNVdaxntbNfzduCD0r3sheRw11MuFJVq6wcpGfWct1t-gT6fdMHPr8WXasZQnI_RTj4txTDNpSREawbop__Q-7TkCdwZDgZYCwZaoNiJcjmVkv1g5hxGm4-GErMGZk6BGQjM_A3MaGj6-Ci9dKPv_7U8JQQAPwFlXn_a5-fZL8j-AfIvoqM</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Kudo, Kei</creator><creator>Nishimura, Takehiro</creator><creator>Izumikawa, Miho</creator><creator>Kozone, Ikuko</creator><creator>Hashimoto, Junko</creator><creator>Fujie, Manabu</creator><creator>Suenaga, Hikaru</creator><creator>Ikeda, Haruo</creator><creator>Satoh, Nori</creator><creator>Shin-ya, Kazuo</creator><general>Springer Japan</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2218-9273</orcidid><orcidid>https://orcid.org/0000-0002-3831-1846</orcidid><orcidid>https://orcid.org/0000-0001-7500-9462</orcidid><orcidid>https://orcid.org/0000-0002-4702-0661</orcidid><orcidid>https://orcid.org/0000-0001-6298-1121</orcidid></search><sort><creationdate>20240501</creationdate><title>Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds</title><author>Kudo, Kei ; 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In developing a heterologous expression system for the large BGCs amenable to the production of such natural products, we selected concanamycin as an appropriate target. We obtained a bacterial artificial chromosome (BAC) clone with a 211-kb insert harboring the entire BGC responsible for the biosynthesis of concanamycin. Heterologous expression of this clone in a host strain,
Streptomyces avermitilis
SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as
ent
-gephyromycin and a novel compound that was designated JBIR-157. We describe herein sequencing and expression studies performed on these BGCs, demonstrating the utility of large BAC clones for the heterologous expression of cryptic or near-silent loci.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>38438499</pmid><doi>10.1038/s41429-024-00711-9</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2218-9273</orcidid><orcidid>https://orcid.org/0000-0002-3831-1846</orcidid><orcidid>https://orcid.org/0000-0001-7500-9462</orcidid><orcidid>https://orcid.org/0000-0002-4702-0661</orcidid><orcidid>https://orcid.org/0000-0001-6298-1121</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 42/40 42/44 45/23 631/326/22/1290 631/326/41/2173 631/92/349 631/92/60 Antibiotics Artificial chromosomes Bacterial artificial chromosomes Bacteriology Biological Products - metabolism Biomedical and Life Sciences Bioorganic Chemistry Biosynthesis Chromosomes, Artificial, Bacterial - genetics Cloning Cloning, Molecular Gene clusters Genes Genomes Life Sciences Medicinal Chemistry Metabolites Microbiology Microorganisms Molecular weight Multigene Family Natural products Organic Chemistry Polyketide Synthases - genetics Polyketide Synthases - metabolism Polyketides Polyketides - metabolism Streptomyces - genetics Streptomyces - metabolism |
| title | Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds |
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