The long-chain, ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential for humans and animals, including marine fish species. Presently, the primary source of these PUFAs is fish oils. As the global production of fish oils appears to be reaching its limits, alternative sources of high-quality ω-3 PUFAs is paramount to support the growing aquaculture industry. Thraustochytrids are a group of heterotrophic protists able to synthesize and accrue large amounts of essential ω-3 PUFAs, including EPA and DHA. Thus, the thraustochytrids are prime candidates to solve the increasing demand for ω-3 PUFAs using microbial cell factories. However, a systems-level understanding of their metabolic shift from cellular growth into lipid accumulation is, to a large extent, unclear. Here, we reconstructed a high-quality genome-scale metabolic model of the thraustochytrid Aurantiochytrium sp. T66 termed iVS1191. Through iterative rounds of model refinement and extensive manual curation, we significantly enhanced the metabolic scope and coverage of the reconstruction from that of previously published models, making considerable improvements with stoichiometric consistency, metabolic connectivity, and model annotations. We show that iVS1191 is highly consistent with experimental growth data, reproducing in vivo growth phenotypes as well as specific growth rates on minimal carbon media. The availability of iVS1191 provides a solid framework for further developing our understanding of T66's metabolic properties, as well as exploring metabolic engineering and process-optimization strategies in silico for increased ω-3 PUFA production.

中文翻译：

---

Aurantiochytrium sp。的高质量基因组规模代谢模型。T66

长链ω -3多不饱和脂肪酸（PUFA）二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）对人类和动物（包括海水鱼类）至关重要。目前，这些PUFA的主要来源是鱼油。随着全球鱼油生产似乎已达到极限，高质量ω -3 PUFA的替代来源对于支持不断发展的水产养殖业至关重要。破囊壶菌是一组异养生物，能够合成并产生大量必需的ω-3 PUFA，包括EPA和DHA。因此，破囊壶菌是解决ω需求增加的主要候选药物-3 PUFA使用微生物细胞工厂。然而，在很大程度上，尚不清楚它们在代谢方面从细胞生长到脂质蓄积的系统级了解。在这里，我们重建了破囊壶菌Aurantiochytrium的高质量基因组规模的代谢模型sp。T66称为iVS1191。通过反复的模型改进和广泛的手动管理，我们从以前发布的模型中大大增强了重建的代谢范围和覆盖范围，在化学计量一致性，代谢连通性和模型注释方面取得了显着改善。我们显示iVS1191与实验生长数据高度一致，可在最小的碳介质上重现体内生长表型以及特定的生长速率。iVS1191的可用性为进一步发展我们对T66的代谢特性的理解以及探索硅的代谢工程和工艺优化策略以增加ω-3 PUFA产量提供了坚实的框架。