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Novel chemobiosynthetic approach for exclusive production of FK506

Paper ID Volume ID Publish Year Pages File Format Full-Text
31627 44825 2012 8 PDF Available
Title
Novel chemobiosynthetic approach for exclusive production of FK506
Abstract

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.

► Streptomyces tsukubaensis produces FK506 together with FK520 as a by-product. ► Inactivation of the allR gene abolishes biosynthesis of FK506 as well as FK520. ► allR encodes a broadly specific enoyl-CoA carboxylase/reductase. ► Feeding allylmalonyl-SNAC to ΔallR strain reestablishes biosynthesis of FK506. ► We describe a chemobiosynthetic procedure for exclusive production of FK506.

Keywords
PKS, polyketide synthase; NRPS, non-ribosomal peptide synthetase; ACP, acyl carrier protein; ccr, crotonyl-CoA reductase/carboxylase; SNAC, N-acetylcysteamine; AT4, acyltransferase domain of the fourth module of FK506 PKS; FK506D, 37,38-dihydro-FK506FK506
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 14, Issue 1, January 2012, Pages 39–46
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us