Natural products (NPs) are considered as a cornerstone for the generation of bioactive leads in drug discovery programs. However, one of the major limitations of NP drug discovery program is “rediscovery” of known compounds, thereby hindering the rate of drug discovery efficiency. Therefore, in recent years, to overcome these limitations, a great deal of attention has been drawn towards understanding the role of microorganisms’ co-culture in inducing novel chemical entities. Such induction could be related to activation of genes which might be silent or expressed at very low levels (below detection limit) in pure-strain cultures under normal laboratory conditions. In this review, chemical diversity of compounds isolated from microbial co-cultures, is discussed. For this purpose, chemodiversity has been represented as a chemical-structure network based on the “Tanimoto Structural Similarity Index”. This highlights the huge structural diversity induced by microbial co-culture. In addition, the current trends in microbial co-culture research are highlighted. Finally, the current challenges (1 - induction monitoring, 2 - reproducibility, 3 - growth time effect and 4 - up-scaling for isolation purposes) are discussed. The information in this review will support researchers to design microbial co-culture strategies for future research efforts. In addition, guidelines for co-culture induction reporting are also provided to strengthen future reporting in this NP field.

在药物发现计划中，天然产物（NP）被认为是产生生物活性线索的基石。但是，NP药物发现计划的主要限制之一是已知化合物的“重新发现”，从而阻碍了药物发现效率的提高。因此，近年来，为了克服这些局限性，已引起人们对理解微生物共培养在诱导新化学实体中的作用的极大关注。这种诱导可能与基因的激活有关，这些基因可能在正常实验室条件下在纯菌株培养物中沉默或以非常低的水平（低于检测限）表达。在这篇综述中，讨论了从微生物共培养物中分离出的化合物的化学多样性。以此目的，化学多样性已被表示为基于“ Tanimoto结构相似性指数”的化学结构网络。这突出了微生物共培养引起的巨大结构多样性。此外，重点介绍了微生物共培养研究的当前趋势。最后，讨论了当前的挑战（1-感应监测，2-重现性，3-生长时间效应和4-放大以达到隔离目的）。这篇综述中的信息将支持研究人员设计微生物共培养策略，以用于未来的研究工作。此外，还提供了共培养诱导报告的指南，以加强该NP领域的未来报告。强调了微生物共培养研究的当前趋势。最后，讨论了当前的挑战（1-感应监测，2-可再现性，3-生长时间效应和4-放大以达到隔离目的）。这篇综述中的信息将支持研究人员设计微生物共培养策略，以用于未来的研究工作。此外，还提供了共培养诱导报告的指南，以加强该NP领域的未来报告。强调了微生物共培养研究的当前趋势。最后，讨论了当前的挑战（1-感应监测，2-可再现性，3-生长时间效应和4-放大以达到隔离目的）。这篇综述中的信息将支持研究人员设计微生物共培养策略，以用于未来的研究工作。此外，还提供了共培养诱导报告的指南，以加强该NP领域的未来报告。