Journal
METABOLIC ENGINEERING
Volume 14, Issue 1, Pages 39-46Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2011.11.003
Keywords
FK506; Allylmalonyl-CoA; Chemobiosynthesis; Streptomyces tsukubaensis; Mutasynthesis; Ethylmalonyl-CoA pathway
Categories
Funding
- Government of Slovenia, Ministry of Higher Education, Science and Technology (Slovenian Research Agency, ARRS) [J4-9331, L4-2188]
- Ministry of the Economy
- JAPTI Agency
- European Social Fund [102/2008]
Ask authors/readers for more resources
FK506, a widely used immunosuppressant, is produced by industrial fermentation processes using various Streptomyces species. Independently of the strain, structurally related compound FK520 is co-produced, resulting in complex and costly isolation procedures. In this paper, we report a chemobiosynthetic approach for exclusive biosynthesis of FK506. This approach is based on the Streptomyces tsukubaensis strain with inactivated allR gene, a homologue of crotonyl-CoA carboxylase/reductase, encoded in the FK506 biosynthetic cluster. This strain produces neither FK506 nor FK520; however, if allylmalonyl-S-N-acetylcysteamine precursor is added to cultivation broth, the production of FK506 is reestablished without FK506-related by-products. Using a combination of metabolic engineering and chemobiosynthetic approach, we achieved exclusive production of FK506, representing a significant step towards development of an advanced industrial bioprocess. (C) 2011 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available