抗微生物耐药性可以被视为一个隐藏的全球性大流行病，必须加强研究以发现新的抗生素。有超过100种生物活性化合物的螺环四酮类聚酮化合物最近因发现了具有不同抗生素活性的噬海豚霉亮菌素而得到增长。选择了三株海洋菌株噬海豚霉亮菌素生产菌（分别命名为CA-214671、CA-214658和CA-218877），并对其进行产量放大和液相色谱/高分辨质谱分析，结果显示它们培养基的乙酸乙酯萃取液中产生了数种之前未被披露的相关化合物。在此，我们报告了两种新的噬海豚霉亮菌素，噬海豚霉亮菌素D和E（1-2），以及已知的噬海豚霉亮菌素，噬海豚霉亮菌素B和C（3-5），还有马克司霉亮菌素（7）和马克司霉亮菌素B（6），后者首次被报道为一种天然产物。对所有分离的化合物进行了对抗多种人类致病菌的测试，结果显示对甲氧西林耐药金黄色葡萄球菌、结核分枝杆菌H37Ra、肠球菌和肠链球菌的活性各异，有的强有力，有的微弱。还评估了它们对人肝腺癌细胞系（Hep G2）的细胞活力，结果显示其细胞毒性弱或无。最后，通过对斑马鱼鼠突胚进行了噬海豚霉亮菌素（3）、噬海豚霉亮菌素B（4）和马克司霉亮菌素（7）的主要化合物的安全性测试，结果显示在浓度为25μM时均没有毒性。

Antimicrobial resistance can be considered a hidden global pandemic and research must be reinforced for the discovery of new antibiotics. The spirotetronate class of polyketides, with more than 100 bioactive compounds described to date, has recently grown with the discovery of phocoenamicins, compounds displaying different antibiotic activities. Three marine Micromonospora strains (CA-214671, CA-214658 and CA-218877), identified as phocoenamicins producers, were chosen to scale up their production and LC/HRMS analyses proved that EtOAc extracts from their culture broths produce several structurally related compounds not disclosed before. Herein, we report the production, isolation and structural elucidation of two new phocoenamicins, phocoenamicins D and E (1-2), along with the known phocoenamicin, phocoenamicins B and C (3-5), as well as maklamicin (7) and maklamicin B (6), the latter being reported for the first time as a natural product. All the isolated compounds were tested against various human pathogens and revealed diverse strong to negligible activity against methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis H37Ra, Enterococcus faecium and Enterococcus faecalis. Their cell viability was also evaluated against the human liver adenocarcinoma cell line (Hep G2), demonstrating weak or no cytotoxicity. Lastly, the safety of the major compounds obtained, phocoenamicin (3), phocoenamicin B (4) and maklamicin (7), was tested against zebrafish eleuthero embryos and all of them displayed no toxicity up to a concentration of 25 μM.