The natural products 6‐deoxyerythronolide B (6dEB), erythromycin D, yersiniabactin (Ybt), and salicylate 2‐O‐β‐d‐glucoside (SAG), representing a range of primary and secondary metabolites generated through heterologous microbial biosynthesis, were analyzed using computational metabolic engineering for the purpose of predicting improved production. Specifically, flux balance analysis allowed for the comprehensive screening of medium components and the determination of single gene deletions that resulted in improved product titers for the target compounds. Outcomes included the identification of amino acids and alternative carbon sources capable of culture medium supplementation for increased cellular production. Separately, Minimization of Metabolic Adjustment and OptForce were used to identify single gene deletion and overexpression targets, respectively, for improvements to the aforementioned biosynthetic schemes. The computational engineering predictions thus provide a starting point for experimental implementation with the goal of improving metabolic carbon flow to the compounds presented in this study, each of which possesses valuable bioactivity. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4208–4217, 2018

中文翻译：

---

基于约束的代谢靶标可提高分子分类中异源化合物的产量

天然产物6-脱氧赤藓醇B（6dEB），红霉素D，耶尔西菌素（Ybt）和水杨酸酯2‐O‐β‐ d葡糖苷（SAG）代表了通过异源微生物生物合成产生的一系列主要和次要代谢产物，使用计算代谢工程进行了分析，目的是预测产量的提高。具体而言，通量平衡分析可对培养基成分进行全面筛选，并确定单基因缺失，从而可提高目标化合物的产品效价。结果包括鉴定能够补充培养基以增加细胞产量的氨基酸和替代碳源。分别地，将代谢调节的最小化和OptForce分别用于鉴定单基因缺失和过表达靶点，以改善上述生物合成方案。因此，计算工程预测为实验实施提供了一个起点，其目标是改善本研究中介绍的化合物的代谢碳流量，每种化合物都具有有价值的生物活性。©2018美国化学工程师学会AIChE J，64：4208–4217，2018