ArticleApplied and environmental microbiology2013
Efficient bioconversion of echinocandin B to its nucleus by overexpression of deacylase genes in different host strains.
Article in Applied and environmental microbiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
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- Cyclic Peptides with Antifungal Properties Derived from Bacteria, Fungi, Plants, and Synthetic Sources.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Natural and Man-Made Cyclic Peptide-Based Antibiotics.Antibiotics (Basel, Switzerland) · 2022Review
- Cyclic peptide drugs approved in the last two decades (2001-2021).RSC chemical biology · 2022Review
- Engineering of Streptomyces lividans for heterologous expression of secondary metabolite gene clusters.Microbial cell factories · 2020Article
- Functional redundancy in Echinocandin B in-cluster transcription factorBiotechnology reports (Amsterdam, Netherlands) · 2018Article
- Draft Genome Sequence of Actinoplanes utahensis NRRL 12052, a Microorganism Involved in Industrial Production of Pharmaceutical Intermediates.Genome announcements · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anidulafungin, which noncompetitively inhibits β-(1,3)-D-glucan synthase in fungal cell wall biosynthesis, is the newest antifungal drug to be developed. Echinocandin B deacylase from Actinoplanes utahensis NRRL 12052 catalyzes the cleavage of the linoleoyl group of echinocandin B, a key step in the process of manufacturing anidulafungin. Unfortunately, the natural yield of echinocandin B nucleus is low. In our study, the echinocandin B deacylase gene was systematically overexpressed by genetic engineering in its original producer, A. utahensis, and in the heterologous hosts Streptomyces lividans TK24 and Streptomyces albus. The introduction of additional copies of the gene, under the control of PermE* or its native promoter, into hosts showed significant increases in its transcription level and in the efficiency of the bioconversion of echinocandin B to its nucleus. The conditions for the cultivation and bioconversion of A. utahensis have been optimized further to improve production. As a result, while the wild-type strain initially produced 0.36 g/liter, a concentration of 4.21 g/liter was obtained after the generation of a strain with additional copies of the gene and further optimization of the reaction conditions. These results are useful for enhancing echinocandin B nucleus production in A. utahensis. Our study could enable the engineering of commercially useful echinocandin B nucleus-overproducing stains.
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