Microbial Synthesis of Human-Hormone Melatonin at Gram Scales.,ACS Synthetic Biology

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Microbial Synthesis of Human-Hormone Melatonin at Gram Scales.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-06-05 , DOI: 10.1021/acssynbio.0c00065
Hao Luo ₁ , Konstantin Schneider ₁ , Ulla Christensen ₁ , Yang Lei ₁ , Markus Herrgard ₁ , Bernhard Ø Palsson _{1,

2,

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Affiliation

Melatonin is a commercially attractive tryptophan-derived hormone. Here we describe a bioprocess for the production of melatonin using Escherichia coli to high titers. The first engineered strain produced 0.13 g/L of melatonin from tryptophan under fed-batch fermentation conditions. A 4-fold improvement on melatonin titer was further achieved by (1) protein engineering of rate-limiting tryptophan hydroxylase to improve 5-hydroxytryptophan biosynthesis and (2) chromosomal integration of aromatic-amino-acid decarboxylase to limit byproduct formation and to minimize gene toxicity to the host cell. Fermentation optimization improved melatonin titer by an additional 2-fold. Deletion of yddG, a tryptophan exporter, exhibited an additive beneficial effect. The final engineered strain produced ∼2.0 g/L of melatonin with tryptophan supplemented externally and ∼1.0 g/L with glucose as the sole carbon source for tryptophan supply. This study lays the foundation for further developing a commercial melatonin-producing E. coli strain.

中文翻译：

克级人激素褪黑素的微生物合成。

褪黑激素是商业上有吸引力的色氨酸衍生激素。在这里，我们描述了使用高滴度大肠杆菌生产褪黑激素的生物过程。在补料分批发酵条件下，第一个工程菌株从色氨酸生产了0.13 g / L的褪黑激素。通过（1）限速色氨酸羟化酶的蛋白质工程来改善5-羟色氨酸的生物合成和（2）芳香族氨基酸脱羧酶的染色体整合以限制副产物的形成并最小化基因，进一步使褪黑激素滴度提高了4倍。对宿主细胞有毒性。发酵优化使褪黑激素效价提高了2倍。删除yddG，一种色氨酸出口商，表现出附加的有益作用。最终的工程菌株产生了约2.0 g / L的褪黑素和外部色氨酸，约1.0 g / L的葡萄糖是唯一的色氨酸供应碳源。这项研究为进一步开发生产褪黑激素的大肠杆菌菌株奠定了基础。

更新日期：2020-06-19

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