Engineering Streptomyces albus B4 for Enhanced Production of (R)-Mellein: A High-Titer Heterologous Biosynthesis Approach,Journal of Agricultural and Food Chemistry

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Engineering Streptomyces albus B4 for Enhanced Production of (R)-Mellein: A High-Titer Heterologous Biosynthesis Approach
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-24 , DOI: 10.1021/acs.jafc.4c02463
Hao Tang ₁ , Wenping Wei ₁ , Jing Wu ₁ , Xingjun Cui ₁ , Wenzong Wang ₁ , Tao Qian ₁ , Jing Wo ₁ , Bang-Ce Ye _{1,

2}

Affiliation

The natural compound (R)-(−)-mellein exhibits antiseptic and fungicidal activities. We investigated its biosynthesis using the polyketide synthase encoded by SACE_5532 (pks8) from Saccharopolyspora erythraea heterologously expressed in Streptomyces albus B4, a chassis chosen for its fast growth, genetic manipulability, and ample large short-chain acyl-CoA precursor supply. High-level heterologous (R)-(−)-mellein yield was achieved by pks8 overexpression and duplication. The precursor supply pathways were strengthened by overexpression of SACE_0028 (encoding acetyl-CoA carboxylase) and four genes involved in β-oxidation (fadD, fadE, fadB, and fadA). Cell growth inhibition by (R)-(−)-mellein production at high concentration was relieved by in situ adsorption using Amberlite XAD16 resin. The final strain, B4mel12, produced (R)-(−)-mellein at 6395.2 mg/L in shake-flask fermentation. Overall, this is the first report of heterologous (R)-(−)-mellein synthesis in microorganism with a high titer. (R)-(−)-mellein prototype in this study opens a possibility for the overproduction of valuable melleins in S. albus B4.

中文翻译：

工程化白色链霉菌 B4 以增强 (R)-Mellein 的生产：一种高滴度异源生物合成方法

天然化合物 ( R )-(−)-mellein 具有防腐和杀菌活性。我们使用来自红色糖多孢菌的SACE_5532 ( pks8 ) 编码的聚酮合酶研究了其生物合成，该酶在白色链霉菌B4 中异源表达，选择该底盘是因为其快速生长、遗传可操作性和充足的大短链酰基辅酶 A 前体供应。通过pks8过表达和复制实现了高水平的异源 ( R )-(−)-mellein 产量。前体供应途径通过SACE_0028 （编码乙酰辅酶A羧化酶）和参与 β-氧化的四个基因（ fadD 、 fadE 、 fadB和fadA ）的过度表达得到加强。使用 Amberlite XAD16 树脂进行原位吸附，可以缓解高浓度 ( R )-(−)-mellein 产生对细胞生长的抑制。最终菌株 B4mel12 在摇瓶发酵中产生了 6395.2 mg/L 的 ( R )-(−)-mellein。总的来说，这是首次报道微生物中高滴度异源 ( R )-(−)-mellein 合成。本研究中的 ( R )-(−)-mellein 原型为S. albus B4 中有价值的 mellein 的过量生产提供了可能性。

更新日期：2024-07-24

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