Abstract
Corynebacterium glutamicum is well known as the amino acid-producing workhorse of fermentation industry, being used for multi-million-ton scale production of glutamate and lysine for more than 60 years. However, it is only recently that extensive research has focused on engineering it beyond the scope of amino acids. Meanwhile, a variety of corynebacterial strains allows access to alternative carbon sources and/or allows production of a wide range of industrially relevant compounds. Some of these efforts set new standards in terms of titers and productivities achieved whereas others represent a proof-of-principle. These achievements manifest the position of C. glutamicum as an important industrial microorganism with capabilities far beyond the traditional amino acid production. In this review we focus on the state of the art of metabolic engineering of C. glutamicum for utilization of alternative carbon sources, (e.g. coming from wastes and unprocessed sources), and construction of C. glutamicum strains for production of new products such as diamines, organic acids and alcohols.
Highlights
Industrial biotechnology is paving the way for a bio-based economy, which is proposed to complement and, in the long term, replace petro-based economy
The metabolic engineering for creating a C. glutamicum xylitol producer included: i) heterologous expression of a C. glutamicum ATCC31831 pentose transporter gene, inserted into the chromosomal DNA to improve direct xylose uptake, ii) heterologous expression of a Candida tenuis gene encoding a single-site mutated xylose reductase (XR) to catalyze xylitol formation, iii) deletion of the lactate dehydrogenase gene to allow use of cofactor utilized in lactic acid formation reaction for xylitol production instead, and iv) deletion of phosphoenolpyruvatedependent fructose phosphotransferase gene and xylulokinase gene (Fig. 1) to prevent formation of xylitol-phosphate which is toxic for cells
An almost three fold increase of methyl 3hydroxybutyrate (MHB) yield could be observed. Deletion of these genes halts the flow through glycolysis, diverts it to pentose phosphate pathway (PPP) and generates a semi-cyclic or cyclic PPP, resulting in an increased cofactor production and availability [95]
Summary
Industrial biotechnology is paving the way for a bio-based economy, which is proposed to complement and, in the long term, replace petro-based economy. Corynebacterium glutamicum is a Gram-positive bacterium and is referred to as the industrial workhorse for amino acid production It was first isolated in 1950s from Japanese soil during a quest for natural L-glutamate producers [1]. After genetic engineering tools were developed, C. glutamicum genome was sequenced and made publically available in 2003 [4,5] and omics technologies such as transcriptome studies evolved [6] These milestones marked the beginning of extensive research efforts to metabolically engineer C. glutamicum, initially for L-glutamate and L-lysine production and later on for the production of a variety of products such as organic acids, alcohols or diamines. Metabolic engineering approaches for Lglutamate and L-lysine production have been reviewed and monographed extensively [7,8,9,10,11,12], and will not be a part of this review
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