Journal
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Volume 102, Issue 23, Pages 9881-9891Publisher
SPRINGER
DOI: 10.1007/s00253-018-9382-x
Keywords
Pneumocandin; Echinocandin; Biosynthesis; Fermentation; Antifungal
Categories
Funding
- National Natural Science Foundation of China (NSFC) [31741004, 31870528]
- National Key R&D Program of China [2018YFD0201202-02]
- University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province [UNPYSCT-2016019]
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Fungal diseases are a global public health problem. Invasive fungal infections pose a serious threat to patients with compromised immune systems, such as those undergoing organ or bone marrow transplants, cancer, or HIV/AIDS. Pneumocandins are antifungal lipohexapeptides of the echinocandin family that noncompetitively inhibit of 1,3--glucan synthase of fungal cell wall and provide the precursor for the semisynthesis of caspofungin, which is widely used as first-line therapy for invasive fungal infections. Recently, the biosynthetic steps leading to formation of pneumocandin B-0 and echinocandin B have been elucidated, and thus, provide a framework and attractive model for further design new antifungal therapeutics around natural variations in echinocandin structural diversities via genetic and chemical tools. In this article, we analyze the biosynthetic pathway of pneumocandins and other echinocandins, provide an update on the array of pneumocandin analogues generated by genetic manipulation, and summarize advances in the enhancement of pneumocandin B-0 production by random mutagenesis and fermentation optimization. We also give offer advice on the development of improved pneumocandin drug candidates and more efficient production of pneumocandin B-0.
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