Branched chain fatty acids (BCFA) are an appealing biorefinery-driven target of fatty acid (FA) production. BCFAs typically have lower melting points compared to straight chain FAs, making them useful in lubricants and biofuels. Actinobacteria, especially Streptomyces species, have unique secondary metabolism that are capable of producing not only antibiotics, but also high percentage of BCFAs in their membrane lipids. Since biosynthesis of polyketide (PK) and FA partially share common pathways to generate acyl-CoA precursors, in theory, Streptomyces sp. with high levels of PK antibiotics production can be easily manipulated into strains producing high levels of BCFAs. To increase the percentage of the BCFA moieties in lipids, we redirected acyl-CoA precursor fluxes from PK into BCFAs using S. coelicolor M1146 (M1146) as a host strain. In addition, 3-ketoacyl acyl carrier protein synthase III and branched chain α-keto acid dehydrogenase were overexpressed to push fluxes of branched chain acyl-CoA precursors towards FA synthesis. The maximum titer of 354.1 mg/L BCFAs, 90.3% of the total FA moieties, was achieved using M1146dD-B, fadD deletion and bkdABC overexpression mutant of M1146 strain. Cell specific yield of 64.4 mg/L/gcell was also achieved. The production titer and specific yield are the highest ever reported in bacterial cells, which provides useful insights to develop an efficient host strain for BCFAs.

中文翻译：

---

工程制链霉菌用于生产单甲基支链脂肪酸。

支链脂肪酸（BCFA）是由生物精炼厂驱动的脂肪酸（FA）生产目标。与直链FA相比，BCFA通常具有较低的熔点，使其可用于润滑剂和生物燃料。放线菌，特别是链霉菌属，具有独特的二次代谢，不仅能够产生抗生素，而且还能在其膜脂中产生高百分比的BCFA。由于聚酮化合物（PK）和FA的生物合成部分共享产生酰基CoA前体的共同途径，因此从理论上讲，链霉菌属（Streptomyces sp。）。PK抗生素含量高的细菌可以很容易地控制成产生BCFA含量高的菌株。为了增加脂质中BCFA部分的百分比，我们使用大肠杆菌S. coelicolor M1146（M1146）作为宿主菌株，将酰基辅酶A前体通量从PK重定向到BCFA中。此外，过表达3-酮酰基酰基载体蛋白合酶III和支链α-酮酸脱氢酶以将支链酰基辅酶A前体的通量推向FA合成。使用M1146菌株的M1146dD-B，fadD缺失和bkdABC过表达突变体，可达到354.1 mg / L BCFA的最大效价，占总FA部分的90.3％。还实现了64.4 mg / L / gcell的细胞比产率。产量效价和比产率是细菌细胞中有史以来最高的，这为开发有效的BCFA宿主菌株提供了有用的见识。M1146菌株的fadD缺失和bkdABC过表达突变体。还实现了64.4 mg / L / gcell的细胞比产率。产量效价和比产率是细菌细胞中有史以来最高的，这为开发有效的BCFA宿主菌株提供了有用的见识。M1146菌株的fadD缺失和bkdABC过表达突变体。还实现了64.4 mg / L / gcell的细胞比产率。产量效价和比产率是细菌细胞中有史以来最高的，这为开发有效的BCFA宿主菌株提供了有用的见识。