9iyw

Structural highlights

Function

GFSA_STRHA First protein in the synthesis of the 16-membered macrolide antibiotics FD-891 and FD-892 (PubMed:20589823). Composed of 5 modules; the first is a loading module (LM) that synthesizes a starter unit used by the first elongation module for polyketide chain elongation (PubMed:34985877, PubMed:37216195). The starter unit is extended by multiple rounds of addition of malonyl-CoA or methylmalonyl-CoA, and other modifications to help generate the final products (Probable) (PubMed:20589823). The loading module (residues 1-927, LM with an inactive acyltransferase domain) preferentially decarboxylates malonyl-GfsA acyl carrier protein of the LM (ACP-LM) over methylmalonyl-GfsA ACP-LM and has no activity on malonyl-CoA or methymalonyl-CoA (PubMed:34985877). LM decarboxylates malonyl-ACP-LM better than the malonyl-ACP-1 module of GfsA (i.e. the next module in the same protein) and has no activity on other malonyl-ACP modules (PubMed:37216195).^{[1] [2] [3] [4]}

References

1. ↑ Kudo F, Motegi A, Mizoue K, Eguchi T. Cloning and characterization of the biosynthetic gene cluster of 16-membered macrolide antibiotic FD-891: involvement of a dual functional cytochrome P450 monooxygenase catalyzing epoxidation and hydroxylation. Chembiochem. 2010 Jul 26;11(11):1574-82. PMID:20589823 doi:10.1002/cbic.201000214
2. ↑ Chisuga T, Nagai A, Miyanaga A, Goto E, Kishikawa K, Kudo F, Eguchi T. Structural Insight into the Reaction Mechanism of Ketosynthase-Like Decarboxylase in a Loading Module of Modular Polyketide Synthases. ACS Chem Biol. 2022 Jan 5. doi: 10.1021/acschembio.1c00856. PMID:34985877 doi:http://dx.doi.org/10.1021/acschembio.1c00856
3. ↑ Chisuga T, Murakami S, Miyanaga A, Kudo F, Eguchi T. Structure-Based Analysis of Transient Interactions between Ketosynthase-like Decarboxylase and Acyl Carrier Protein in a Loading Module of Modular Polyketide Synthase. ACS Chem Biol. 2023 May 22. PMID:37216195 doi:10.1021/acschembio.3c00151
4. ↑ Kudo F, Motegi A, Mizoue K, Eguchi T. Cloning and characterization of the biosynthetic gene cluster of 16-membered macrolide antibiotic FD-891: involvement of a dual functional cytochrome P450 monooxygenase catalyzing epoxidation and hydroxylation. Chembiochem. 2010 Jul 26;11(11):1574-82. PMID:20589823 doi:10.1002/cbic.201000214