ArticleApplied microbiology and biotechnology2023
Optimization of FK-506 production in Streptomyces tsukubaensis by modulation of Crp-mediated regulation.
Article in Applied microbiology and biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Discovery of MBL-AB01: a novel antibacterial xanthone antibiotic with high activity against methicillin-resistantApplied and environmental microbiology · 2026Article
- Diverse chemotypes of polyketides as promising antimicrobial agents: latest progress.RSC advances · 2025Review
- Enhancement of tacrolimus production in Streptomyces tsukubaensis by genetic engineering and process optimization.World journal of microbiology & biotechnology · 2025Article
- Regulatory orchestration of FK506 biosynthesis iniScience · 2025Article
- Overexpression of the Wbl family regulator whiDWorld journal of microbiology & biotechnology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
FK-506 is a potent immunosuppressive macrocyclic polyketide with growing pharmaceutical interest, produced by Streptomyces tsukubaensis. However, due to low levels synthesized by the wild-type strain, biotechnological production of FK-506 is rather limited. Optimization strategies to enhance the productivity of S. tsukubaensis by means of genetic engineering have been established. In this work primarily global regulatory aspects with respect to the FK-506 biosynthesis have been investigated with the focus on the global Crp (cAMP receptor protein) regulator. In expression analyses and protein-DNA interaction studies, the role of Crp during FK-506 biosynthesis was elucidated. Overexpression of Crp resulted in two-fold enhancement of FK-506 production in S. tsukubaensis under laboratory conditions. Further optimizations using fermentors proved that the strategy described in this study can be transferred to industrial scale, presenting a new approach for biotechnological FK-506 production. KEY POINTS: • The role of the global Crp (cAMP receptor protein) regulator for FK-506 biosynthesis in S. tsukubaensis was demonstrated • Crp overexpression in S. tsukubaensis was applied as an optimization strategy to enhance FK-506 and FK-520 production resulting in two-fold yield increase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.