对微生物的利用经历了天然混合培养、纯培养到有目的的共培养阶段。目前，对微生物共培养适应的研究较少且主要集中在种间互作。纤维堆囊菌是一类具有复杂细胞群体行为和丰富次级代谢产物的大基因组细菌类群。我们前期研究表明，纤维堆囊菌菌株间共培养会导致生物量降低，但次级代谢产物埃博霉素产量会上升，并且埃博霉素类型要比单独培养时丰富。进一步研究发现不同菌株的基因组大小差异可达5Mbp(9.81-14.78)。本项目在前期工作基础上，拟对不同纤维堆囊菌菌株组合进行共培养连续传代，分析建立稳定共培养关系的生长性状和埃博霉素产生的变化；通过基因组重测序和链特异性转录组分析共培养过程的基因组变异和转录变化，了解种内互作过程中的基因组及转录组共适应模式，认识菌株共培养造成埃博霉素产量提高和结构修饰的原因。研究结果对了解微生物种内互作的模式有重要意义，并为通过共培养发现纤维堆囊菌中新天然活性产物和提高产量提供借鉴

The use of microorganisms has gone through three stages, namely the natural mixed cultivation, pure cultivation and co-cultivation. At present, co-cultivation has been less studied, and is mainly performed between inter-species microorganisms. Sporangium cellulosum is bacterial group with complex social behaviors, rich secondary metabolites, and big genomes. Our previous studies shows that co-cultivations of different S.cellulosum strains reduced the total biomass significantly. However, compared to the pure-cultivation, co-cultivation were able to increase the yield and produce more analogues of secondary metabolites epothilones. Genome sequencing indicated that different S.cellulosum strains varied their genome sizes markedly, ranging from 9.81 Mbp to 14.78 Mbp. In this project, we will sub-cultivate different pair-groups of S.cellulosum strains to establish stable co-cultivation relationships, analyze the characteristics of growth and changes of epothilones in the sub-cultures. We will analyze the changes of genome and transcriptional mode in sub-cultures of different S.cellulosum strains using genome resequencing and strand-specific RNA-Seq. The results will help us to understand the mode of intra-species interaction in microorganism, and provide insights in the mix-cultivation of different S.cellulosum strains.