Abstract
The term vitamin B6 is a designation for the vitamers pyridoxal, pyridoxamine, pyridoxine and the respective phosphate esters pyridoxal-5′-phosphate (PLP), pyridoxamine-5′-phosphate and pyridoxine-5′-phosphate. Animals and humans are unable to synthesise vitamin B6. These organisms have to take up vitamin B6 with their diet. Therefore, vitamin B6 is of commercial interest as a food additive and for applications in the pharmaceutical industry. As yet, two naturally occurring routes for de novo synthesis of PLP are known. Both routes have been genetically engineered to obtain bacteria overproducing vitamin B6. Still, major genetic engineering efforts using the existing pathways are required for developing fermentation processes that could outcompete the chemical synthesis of vitamin B6. Recent suppressor screens using mutants of the Gram-negative and Gram-positive model bacteria Escherichia coli and Bacillus subtilis, respectively, carrying mutations in the native pathways or heterologous genes uncovered novel routes for PLP biosynthesis. These pathways consist of promiscuous enzymes and enzymes that are already involved in vitamin B6 biosynthesis. Thus, E. coli and B. subtilis contain multiple promiscuous enzymes causing a so-called underground metabolism allowing the bacteria to bypass disrupted vitamin B6 biosynthetic pathways. The suppressor screens also show the genomic plasticity of the bacteria to suppress a genetic lesion. We discuss the potential of the serendipitous pathways to serve as a starting point for the development of bacteria overproducing vitamin B6.Key points• Known vitamin B6 routes have been genetically engineered.• Underground metabolism facilitates the emergence of novel vitamin B6 biosynthetic pathways.• These pathways may be suitable to engineer bacteria overproducing vitamin B6.
Highlights
The term vitamin B6 collectively designates the vitamers pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN) and the respective phosphate esters pyridoxal-5′-phosphate (PLP), pyridoxamine-5′-phosphate (PMP) and pyridoxine-5′-phosphate (PNP)(Rosenberg 2012) (Fig. 1a)
This review intends to describe novel and hybrid vitamin B6 biosynthetic routes that have been identified via genetic suppressor screens using mutants of the Gram-negative and Gram-positive model bacteria Escherichia coli and B. subtilis, respectively, carrying mutations in the native genes required for synthesising the essential B6 vitamer PLP
Several native enzymes are present in B. subtilis that could be part of the novel serendipitous DXP-dependent vitamin B6 pathway (Fig. 3). While it is rather unclear how the YtoQ protein of unknown function enables the evolved B. subtilis to employ the PdxH and PdxJ enzyme to produce PLP, the lack of bacillithiol could be beneficial because the thiol was shown to inactivate the 3PG dehydrogenase SerA by binding to the cysteine residue 410 in the active site (Chi et al 2011; Chi et al 2013) the loss of bacillithiol biosynthesis could enhance the promiscuous activity of SerA in the bacteria
Summary
The term vitamin B6 collectively designates the vitamers pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN) and the respective phosphate esters pyridoxal-5′-phosphate (PLP), pyridoxamine-5′-phosphate (PMP) and pyridoxine-5′-phosphate (PNP)(Rosenberg 2012) (Fig. 1a). This review intends to describe novel and hybrid vitamin B6 biosynthetic routes that have been identified via genetic suppressor screens using mutants of the Gram-negative and Gram-positive model bacteria Escherichia coli and B. subtilis, respectively, carrying mutations in the native genes required for synthesising the essential B6 vitamer PLP.
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