Liu Shuo, Xiao Fei, Lv Lanxin, Wang Meiyan, Li Wenli, Niu Guoqing
College of Agronomy and Biotechnology, Southwest University, Chongqing, 400715, China.
Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
Synth Syst Biotechnol. 2025 May 26;10(3):1059-1069. doi: 10.1016/j.synbio.2025.05.010. eCollection 2025 Sep.
The genus exhibits a complex life cycle of morphological differentiation and an extraordinary capacity to produce numerous bioactive secondary metabolites. In submerged cultures, species usually grow in the form of mycelial networks and aggregate into large pellets or clumps, which is generally unfavorable for industrial production. This study aimed to construct efficient microbial cell factories by manipulating morphology-related genes. We herein employed a morphology engineering approach to generate eight engineered derivatives (MECS01∼MECS08) of M1146, a versatile chassis widely used for the heterologous production of various secondary metabolites. We found that genetic manipulation of morphology-related genes exerted a substantial influence on the growth and mycelial characteristics of the engineered strains. Once the native actinorhodin gene cluster was introduced into these strains, antibiotic production increased in all engineered strains compared to the parental strain. Notably, a significant elevation of actinorhodin production was observed in three of the engineered strains, MECS01, MECS03 and MECS05. Similar scenarios occurred when expressing the staurosporine gene cluster and the carotenoid gene cluster in these three engineered derivatives, respectively. Our study demonstrates that morphology engineering represents an effective strategy for alleviating mycelial aggregation. It has also expanded the toolkit of chassis available for the heterologous expression of gene clusters encoding a variety of secondary metabolites.
该属表现出形态分化的复杂生命周期以及产生大量生物活性次生代谢产物的非凡能力。在深层培养中，该属物种通常以菌丝网络的形式生长并聚集成大的颗粒或团块，这通常不利于工业生产。本研究旨在通过操纵与形态相关的基因构建高效的微生物细胞工厂。我们在此采用形态工程方法，构建了M1146的八个工程衍生物（MECS01∼MECS08），M1146是一种广泛用于多种次生代谢产物异源生产的通用底盘。我们发现，对与形态相关基因的遗传操纵对工程菌株的生长和菌丝特征产生了重大影响。一旦将天然放线紫红素基因簇引入这些菌株，与亲本菌株相比，所有工程菌株的抗生素产量均有所增加。值得注意的是，在三个工程菌株MECS01、MECS03和MECS05中观察到放线紫红素产量显著提高。当分别在这三个工程衍生物中表达星形孢菌素基因簇和类胡萝卜素基因簇时，也出现了类似的情况。我们的研究表明，形态工程是减轻菌丝聚集的有效策略。它还扩展了可用于编码多种次生代谢产物的基因簇异源表达的底盘工具集。
