Presentation Information
[P01-086]Rare and Highly Specific Butenolide Signals Induce Antibiotic Production in Streptomyces rochei
○Aiko Teshima1, Asahi Hirata1, Miho Sumiyoshi1, Hazuki Fujita1, Momoko Akimoto1, Mary Hannah Rose A. Padayao1, Yuto Eguchi1, Maki Matsuura2, Miyuki Otsuka2, Kunimobu Inada1, Kenji Arakawa1 (1. Hiroshima Univ. (Japan), 2. Tamagawa Univ. (Japan))
Keywords:
Streptomyces,signaling molecules,butenolide,antibiotic induction,structure–activity relationship
Signaling molecules induce secondary metabolite production and morphological differentiation in Streptomycesspecies. For example, the well-studied signaling molecule A-factor induces streptomycin production in Streptomyces griseus.
Streptomyces rochei 7434AN4 produces two structurally unrelated polyketide antibiotics, lankacidin (LC) and lankamycin (LM). Their biosynthesis is tightly controlled by signaling molecules termed Streptomyces rochei butenolides (SRBs), which are biosynthesized by the SRB synthase SrrX.
In terms of structural diversity, approximately 60% of Streptomyces strains are estimated to produce γ-butyrolactone-type signaling molecules. However, the distribution and structural requirements of SRB-type butenolides in Streptomyces species remain unclear. This study aimed to investigate their distribution and functional specificity.
We analyzed 122 randomly selected Streptomyces strains using feeding extract and co-fermentation assays with the srrX-deficient strain KA20. None of the donor strains, except Streptomyces cellostaticus (a producer of LC and LM), failed to restore LC and LM production in strain KA20. These findings indicate the rare distribution of SRB-type butenolides and suggest strict structural requirements for their signaling activity.
We also explored the structure–activity relationship of SRB molecules. Synthetic analogs, such as SAB1 (a shorter-chain variant) and 4-dehydroxy-SRB1, were tested for their ability to induce antibiotic production. Neither compound showed activity, even at significantly higher concentrations than natural SRB1. These results indicate that both the length of the hydrocarbon chain at the C-2 position and the presence of a hydroxyl group at the C-4 position are essential for biological activity.
In conclusion, SRB-type butenolides represent a rare and highly selective signaling system in Streptomyces species. In general, Streptomyces species possess multiple homologs of signaling molecules receptors (for example, seven receptor homologs in S. rochei). It is likely that SRB-type signaling molecule can induce biosynthetic gene clusters (BGCs) in other Streptomyces strains. Future studies will aim to determine whether SRBs can induce secondary metabolite production in other Streptomyces species.
[Reference]
Asahi Hirata†, Miho Sumiyoshi†, Hazuki Fujita, Momoko Akimoto, Mary Hannah Rose A. Padayao, Yuto Eguchi, Maki Matsuura, Miyuki Otsuka, Kuninobu Inada, Aiko Teshima, and Kenji Arakawa. “Rare distribution of butenolide-type signaling molecules among Streptomyces strains and functional importance as inducing factors for secondary metabolite production in Streptomyces rochei 7434AN4” The Journal of Antibiotics, 78, 488-499 (2025).
Streptomyces rochei 7434AN4 produces two structurally unrelated polyketide antibiotics, lankacidin (LC) and lankamycin (LM). Their biosynthesis is tightly controlled by signaling molecules termed Streptomyces rochei butenolides (SRBs), which are biosynthesized by the SRB synthase SrrX.
In terms of structural diversity, approximately 60% of Streptomyces strains are estimated to produce γ-butyrolactone-type signaling molecules. However, the distribution and structural requirements of SRB-type butenolides in Streptomyces species remain unclear. This study aimed to investigate their distribution and functional specificity.
We analyzed 122 randomly selected Streptomyces strains using feeding extract and co-fermentation assays with the srrX-deficient strain KA20. None of the donor strains, except Streptomyces cellostaticus (a producer of LC and LM), failed to restore LC and LM production in strain KA20. These findings indicate the rare distribution of SRB-type butenolides and suggest strict structural requirements for their signaling activity.
We also explored the structure–activity relationship of SRB molecules. Synthetic analogs, such as SAB1 (a shorter-chain variant) and 4-dehydroxy-SRB1, were tested for their ability to induce antibiotic production. Neither compound showed activity, even at significantly higher concentrations than natural SRB1. These results indicate that both the length of the hydrocarbon chain at the C-2 position and the presence of a hydroxyl group at the C-4 position are essential for biological activity.
In conclusion, SRB-type butenolides represent a rare and highly selective signaling system in Streptomyces species. In general, Streptomyces species possess multiple homologs of signaling molecules receptors (for example, seven receptor homologs in S. rochei). It is likely that SRB-type signaling molecule can induce biosynthetic gene clusters (BGCs) in other Streptomyces strains. Future studies will aim to determine whether SRBs can induce secondary metabolite production in other Streptomyces species.
[Reference]
Asahi Hirata†, Miho Sumiyoshi†, Hazuki Fujita, Momoko Akimoto, Mary Hannah Rose A. Padayao, Yuto Eguchi, Maki Matsuura, Miyuki Otsuka, Kuninobu Inada, Aiko Teshima, and Kenji Arakawa. “Rare distribution of butenolide-type signaling molecules among Streptomyces strains and functional importance as inducing factors for secondary metabolite production in Streptomyces rochei 7434AN4” The Journal of Antibiotics, 78, 488-499 (2025).
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