Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum

Astaxanthin, a red C40 carotenoid, is one of the most abundant marine carotenoids. It is currently used as a food and feed additive in a hundred-ton scale and is furthermore an attractive component for pharmaceutical and cosmetic applications with antioxidant activities. Corynebacterium glutamicum,...

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Main Authors: Nadja A. Henke, Sabine A. E. Heider, Petra Peters-Wendisch, Volker F. Wendisch
Format: Article
Language:English
Published: MDPI AG 2016-06-01
Series:Marine Drugs
Subjects:
Online Access:http://www.mdpi.com/1660-3397/14/7/124
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author Nadja A. Henke
Sabine A. E. Heider
Petra Peters-Wendisch
Volker F. Wendisch
author_facet Nadja A. Henke
Sabine A. E. Heider
Petra Peters-Wendisch
Volker F. Wendisch
author_sort Nadja A. Henke
collection DOAJ
description Astaxanthin, a red C40 carotenoid, is one of the most abundant marine carotenoids. It is currently used as a food and feed additive in a hundred-ton scale and is furthermore an attractive component for pharmaceutical and cosmetic applications with antioxidant activities. Corynebacterium glutamicum, which naturally synthesizes the yellow C50 carotenoid decaprenoxanthin, is an industrially relevant microorganism used in the million-ton amino acid production. In this work, engineering of a genome-reduced C. glutamicum with optimized precursor supply for astaxanthin production is described. This involved expression of heterologous genes encoding for lycopene cyclase CrtY, β-carotene ketolase CrtW, and hydroxylase CrtZ. For balanced expression of crtW and crtZ their translation initiation rates were varied in a systematic approach using different ribosome binding sites, spacing, and translational start codons. Furthermore, β-carotene ketolases and hydroxylases from different marine bacteria were tested with regard to efficient astaxanthin production in C. glutamicum. In shaking flasks, the C. glutamicum strains developed here overproduced astaxanthin with volumetric productivities up to 0.4 mg·L−1·h−1 which are competitive with current algae-based production. Since C. glutamicum can grow to high cell densities of up to 100 g cell dry weight (CDW)·L−1, the recombinant strains developed here are a starting point for astaxanthin production by C. glutamicum.
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spelling doaj.art-9897503f366c4079ad2d94b713ace22e2022-12-22T02:53:32ZengMDPI AGMarine Drugs1660-33972016-06-0114712410.3390/md14070124md14070124Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicumNadja A. Henke0Sabine A. E. Heider1Petra Peters-Wendisch2Volker F. Wendisch3Genetics of Prokaryotes, Faculty of Biology & CeBiTec, Bielefeld University, Bielefeld D-33615, GermanyGenetics of Prokaryotes, Faculty of Biology & CeBiTec, Bielefeld University, Bielefeld D-33615, GermanyGenetics of Prokaryotes, Faculty of Biology & CeBiTec, Bielefeld University, Bielefeld D-33615, GermanyGenetics of Prokaryotes, Faculty of Biology & CeBiTec, Bielefeld University, Bielefeld D-33615, GermanyAstaxanthin, a red C40 carotenoid, is one of the most abundant marine carotenoids. It is currently used as a food and feed additive in a hundred-ton scale and is furthermore an attractive component for pharmaceutical and cosmetic applications with antioxidant activities. Corynebacterium glutamicum, which naturally synthesizes the yellow C50 carotenoid decaprenoxanthin, is an industrially relevant microorganism used in the million-ton amino acid production. In this work, engineering of a genome-reduced C. glutamicum with optimized precursor supply for astaxanthin production is described. This involved expression of heterologous genes encoding for lycopene cyclase CrtY, β-carotene ketolase CrtW, and hydroxylase CrtZ. For balanced expression of crtW and crtZ their translation initiation rates were varied in a systematic approach using different ribosome binding sites, spacing, and translational start codons. Furthermore, β-carotene ketolases and hydroxylases from different marine bacteria were tested with regard to efficient astaxanthin production in C. glutamicum. In shaking flasks, the C. glutamicum strains developed here overproduced astaxanthin with volumetric productivities up to 0.4 mg·L−1·h−1 which are competitive with current algae-based production. Since C. glutamicum can grow to high cell densities of up to 100 g cell dry weight (CDW)·L−1, the recombinant strains developed here are a starting point for astaxanthin production by C. glutamicum.http://www.mdpi.com/1660-3397/14/7/124astaxanthin productioncarotenoidsgenome-reduced Corynebacterium glutamicumsystematic approachmetabolic engineering
spellingShingle Nadja A. Henke
Sabine A. E. Heider
Petra Peters-Wendisch
Volker F. Wendisch
Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum
Marine Drugs
astaxanthin production
carotenoids
genome-reduced Corynebacterium glutamicum
systematic approach
metabolic engineering
title Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum
title_full Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum
title_fullStr Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum
title_full_unstemmed Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum
title_short Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum
title_sort production of the marine carotenoid astaxanthin by metabolically engineered corynebacterium glutamicum
topic astaxanthin production
carotenoids
genome-reduced Corynebacterium glutamicum
systematic approach
metabolic engineering
url http://www.mdpi.com/1660-3397/14/7/124
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