异源表达来自<italic style="font-style: italic">Streptomyces </italic>sp. CB03234的气囊合成基因簇强化<italic style="font-style: italic">Streptomyces albus </italic>J1074合成多种天然产物

王一帆; 王欣然; 陈宁辛; 罗小舟

doi:10.12211/2096-8280.2025-072

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异源表达来自Streptomyces sp. CB03234的气囊合成基因簇强化Streptomyces albus J1074合成多种天然产物

研究论文 | 更新时间：2025-12-30

- 异源表达来自Streptomyces sp. CB03234的气囊合成基因簇强化Streptomyces albus J1074合成多种天然产物
- Heterologous expression of gas vesicle biosynthetic gene cluster from Streptomyces sp. CB03234 enhances biosynthesis of diverse natural products in Streptomyces albus J1074
- 合成生物学 2025年页码：1-13
- 作者机构：
  
  1.喀什大学生命与地理科学学院，新疆帕米尔高原生物资源与生态重点实验室，新疆喀什 844000
  2.中国科学院深圳先进技术研究院，合成生物学研究所，合成生物化学研究中心，广东深圳 518055
  3.中国科学院深圳先进技术研究院，定量合成生物学全国重点实验室，深圳合成生物学创新研究院，广东深圳 518055
- 作者简介：
  
  王一帆（1999—），女，硕士研究生。研究方向为链霉菌来源天然产物的合成生物学与代谢工程研究。
  罗小舟（1987—），男，研究员，博士生导师。研究方向为酶的定向化、蛋白质工程、高通量筛选以及天然及非天然化合物的生物全合成。
- 基金信息：
  
  国家自然科学基金资助项目(32470029);深圳市医学研究专项资金(D2301005);深圳市科技计划(JCYJ20220531100207017;KJZD20230923115906013);中国科学院深圳先进技术研究院杰青计划(E4G021)
- DOI：10.12211/2096-8280.2025-072
  中图分类号： Q819
- 收稿：2025-07-11，
  
  修回：2025-12-23，
  
  网络首发：2025-12-30，
- 稿件说明：
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王一帆，王欣然，陈宁辛，罗小舟. 异源表达来自Streptomyces sp. CB03234的气囊合成基因簇强化Streptomyces albus J1074合成多种天然产物［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-072

WANG Yifan， WANG Xinran， CHEN Ningxin， LUO Xiaozhou. Heterologous expression of gas vesicle biosynthetic gene cluster from Streptomyces sp. CB03234 enhances biosynthesis of diverse natural products in Streptomyces albus J1074［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-072
王一帆，王欣然，陈宁辛，罗小舟. 异源表达来自Streptomyces sp. CB03234的气囊合成基因簇强化Streptomyces albus J1074合成多种天然产物［J］. 合成生物学， 2025， 6. DOI： 10.12211/2096-8280.2025-072 DOI：

WANG Yifan， WANG Xinran， CHEN Ningxin， LUO Xiaozhou. Heterologous expression of gas vesicle biosynthetic gene cluster from Streptomyces sp. CB03234 enhances biosynthesis of diverse natural products in Streptomyces albus J1074［J］. Synthetic Biology Journal， 2025， 6. DOI： 10.12211/2096-8280.2025-072 DOI：

摘要

气囊（Gas Vesicles）是一类由蛋白质构成的刚性中空细胞器，常见于水生微生物，由其基因组内完整的气囊合成基因簇编码组装而成。值得注意的是，同源的气囊基因簇也广泛分布于土壤链霉菌中，但其生理功能尚未明确。本研究克隆出来自链霉菌

Streptomyces

sp. CB03234 的气囊基因簇

gvpOAFGJLSK

（

gvp3234

，3.4 kb），并通过接合转移技术将其导入模式链霉菌

Streptomyces albus

J1074 中。透射电子显微镜（TEM）观察未在重组菌株中检测到典型气囊结构，但发现异源表达

gvp3234

能显著促进宿主菌的早期生长，并引发代谢组的广泛重编程。非靶向代谢组学分析表明，重组菌株中有170种代谢物的积累水平显著上调。通过与数据库比对，确认了包括2-氨基苯甲酸、Albaflavenone在内的多种已知活性物质的产量大幅提高，并鉴定出22种被激活的未知代谢物。此外，在另一株链霉菌

Streptomyces venezuelae

ISP5230 中异源表达

gvp3234

，同样观察到了代谢组的显著变化及沉默代谢途径的激活。研究进一步发现，异源表达

gvp3234

还能有效增强异源酶蛋白的合成效率。本研究首次报道了异源表达气囊基因簇

gvp3234

在两株链霉菌中具有提升已知代谢产物产量、激活宿主沉默代谢途径的普适性功能，为链霉菌代谢工程中目标产物的理性优化及新型活性分子的挖掘提供了新的工具与理论依据。

Abstract

Gas vesicles (GVs) are a class of protein-based

rigid

hollow organelles commonly found in aquatic microorganisms. They are assembled from gene clusters encoding complete gas vesicle synthesis pathways within the genome. Notably

homologous gas vesicle gene clusters are also widely distributed in soil streptomycetes

though their physiological functions remain unclear. In this study

we cloned the gas vesicle gene cluster

gvpOAFGJLSK

(

gvp3234

3.4 kb) from

Streptomyces

sp. CB03234 and introduced it into the model streptomycete

Streptomyces albus

J1074 via conjugative transfer. Although transmission electron microscopy (TEM) observations did not detect typical gas vesicle structures in the recombinant strain

heterologous expression of

gvp3234

was found to significantly promote early growth of the host strain and trigger extensive metabolic reprogramming. Untargeted metabolomics analysis revealed that the accumulation levels

of 170 metabolites were significantly upregulated in the recombinant strain. By comparison with databases

we confirmed a substantial increase in the production of various known bioactive compounds

including 2-aminobenzoic acid and albaflavenone

and identified 22 previously uncharacterized metabolites that were activated. Furthermore

heterologous expression of

gvp3234

in another streptomycete

Streptomyces venezuelae

ISP5230

also led to significant changes in the metabolome and activation of silent metabolic pathways. The study further demonstrated that heterologous expression of

gvp3234

effectively enhanced the synthesis efficiency of heterologous enzyme proteins. This study is the first to report that heterologous expression of the gas vesicle gene cluster

gvp3234

exhibits a universal function in two species of streptomycetes

enhancing the production of known metabolites and activating silent metabolic pathways in the host. These findings provide a novel tool and theoretical foundation for the rational optimization of target products and the discovery of new bioactive molecules in streptomycete metabolic engineering.

关键词

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异源表达来自Streptomyces sp. CB03234的气囊合成基因簇强化Streptomyces albus J1074合成多种天然产物

Heterologous expression of gas vesicle biosynthetic gene cluster from Streptomyces sp. CB03234 enhances biosynthesis of diverse natural products in Streptomyces albus J1074

DOI：10.12211/2096-8280.2025-072

摘要

Abstract

关键词

Keywords

references