Myxococcota represents a small bacterial phylum comprising seven families, which have been shown to be exceptionally rich producers of pharmaceutically interesting natural products. Because of the challenging microbiology of most Myxococcota, their cultured biodiversity is scarcely explored. This study introduces a divergent myxobacterial family, called Pendulisporaceae, with distinct sporulation behavior. Strikingly, 90% of their biosynthetic gene clusters have not been assigned to their respective products and are distinct from published gene-cluster families. The encoded biosynthetic machineries exhibit unprecedented chemistry and enzymology, including the first prokaryotic non-ribosomal peptide synthetase acetylation domain and a triple hybrid nonribosomal peptide-polyketide-terpene pathway. Isolated novel products of the latter, alongside a sorangicin antibiotic derivative, exhibit potent inhibition of a human pathogenic coronavirus and multidrug-resistant Staphylococcus aureus. Through description of the four Pendulispora strains, we expand the publicly available myxobacterial gene-cluster families by a striking 9% and enable further studies on myxobacterial sporulation.

粘球菌门代表了一个由七个科组成的小型细菌门，这些科已被证明是具有药学意义的天然产物的极其丰富的生产者。由于大多数粘球菌具有挑战性的微生物学，它们的培养生物多样性很少被探索。这项研究介绍了一种不同的粘细菌家族，称为摆孢菌科，具有独特的孢子形成行为。引人注目的是，他们 90% 的生物合成基因簇尚未分配给各自的产品，并且与已发表的基因簇家族不同。编码的生物合成机器表现出前所未有的化学和酶学，包括第一个原核非核糖体肽合成酶乙酰化结构域和三重混合非核糖体肽-聚酮化合物-萜烯途径。后者的分离新产品与索兰霉素抗生素衍生物一起，对人类致病性冠状病毒和多重耐药金黄色葡萄球菌表现出有效的抑制作用。通过对四种Pendulispora菌株的描述，我们将公开的粘细菌基因簇家族扩大了惊人的 9%，并使得对粘细菌孢子形成的进一步研究成为可能。