Improved fermentative production of gamma-aminobutyric acid via the putrescine route: Systems metabolic engineering for production from glucose, amino sugars, and xylose
Improved fermentative production of gamma-aminobutyric acid via the putrescine route: Systems metabolic engineering for production from glucose, amino sugars, and xylose
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DOI：
10.1002/bit.26211
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发表时间：
2017-04-01
影响因子：
3.8
通讯作者：
Wendisch, Volker F.
中科院分区：
文献类型：
--
作者：
Jorge, Joao M. P.;Nguyen, Anh Q. D.;Wendisch, Volker F.
γ -氨基丁酸（GABA）是一种广泛存在于自然界的非蛋白氨基酸。在GABA的多种用途中，其内酰胺形式的2-吡咯烷酮可以化学转化为可生物降解的塑料聚酰胺-4。在代谢过程中，氨基丁酸可以通过谷氨酸脱羧或从腐胺转氨化开始的途径合成。重组谷氨酸棒状杆菌从葡萄糖发酵生产GABA已经通过这两种途径进行了描述。以腐胺为基础的GABA生产的特点是副产物如n -乙酰腐胺的积累。它们的形成被精子（di）ne n -乙酰转移酶基因snaA的缺失所破坏。为了改善l-谷氨酸作为前体的供应，通过将2-氧戊二酸脱氢酶亚基e10的染色体基因的翻译起始密码子改变为较不受欢迎的TTG，并通过将氨基酸残基15从苏氨酸改变为丙氨酸来维持抑制蛋白OdhI的抑制形式，降低了2-氧戊二酸脱氢酶的活性。本文所述菌株以腐胺为基础生产GABA，在补料分批培养中，GABA滴度高达63.2gL(-1)，最大体积生产力高达1.34gL(-1)h(-1)，这是迄今为止报道的发酵GABA生产的最高体积生产力。此外，从碳源木糖、氨基葡萄糖和n -乙酰氨基葡萄糖生产GABA，这些碳源在食品或饲料工业中没有竞争用途。Biotechnol。Bioeng。2017;114: 862 - 873。(c) 2016 Wiley Periodicals, Inc.；
Gamma-aminobutyric acid (GABA) is a non-protein amino acid widespread in Nature. Among the various uses of GABA, its lactam form 2-pyrrolidone can be chemically converted to the biodegradable plastic polyamide-4. In metabolism, GABA can be synthesized either by decarboxylation of l-glutamate or by a pathway that starts with the transamination of putrescine. Fermentative production of GABA from glucose by recombinant Corynebacterium glutamicum has been described via both routes. Putrescine-based GABA production was characterized by accumulation of by-products such as N-acetyl-putrescine. Their formation was abolished by deletion of the spermi(di)ne N-acetyl-transferase gene snaA. To improve provision of l-glutamate as precursor 2-oxoglutarate dehydrogenase activity was reduced by changing the translational start codon of the chromosomal gene for 2-oxoglutarate dehydrogenase subunit E1o to the less preferred TTG and by maintaining the inhibitory protein OdhI in its inhibitory form by changing amino acid residue 15 from threonine to alanine. Putrescine-based GABA production by the strains described here led to GABA titers up to 63.2gL(-1) in fed-batch cultivation at maximum volumetric productivities up to 1.34gL(-1)h(-1), the highest volumetric productivity for fermentative GABA production reported to date. Moreover, GABA production from the carbon sources xylose, glucosamine, and N-acetyl-glucosamine that do not have competing uses in the food or feed industries was established. Biotechnol. Bioeng. 2017;114: 862-873. (c) 2016 Wiley Periodicals, Inc.