Heterologous production of capreomycin and generation of new capreomycin derivatives through metabolic engineering
AssigneeWisconsin Alumni Research Foundation
InventorsMichael George Thomas, Elizabeth Anne Felnagle, Michelle Renee Rondon, Andrew David Berti
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Abstract
Provided are nucleic acid molecules comprising at least a functional fragment of the capreomycin biosynthetic gene cluster, polypeptides encoded by the cluster and recombinant host cells transformed with any of the nucleic acid molecules disclosed herein. Various methods using any of the vectors or expression cassettes that encode one or more of the gene products of the cluster are provided for heterologous production of capreomycin and capreomycin derivatives.
Claims25
An isolated and purified nucleic acid molecule that encodes a Capreomycin A (CmnA) gene product having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:2, wherein the CmnA gene product is a non-ribosomal peptide synthetase product capable of forming a peptide bond between a peptide that comprises L-2,3-diaminopropionate and L-serine or L-alanine.
An isolated and purified nucleic acid molecule that encodes a polypeptide having the amino acid sequence set forth in SEQ ID NO:2 (CmnA) and which further encodes a polypeptide selected from one or more of the group consisting of SEQ ID NO:3 (CmnB), SEQ ID NO:4 (CmnC), SEQ ID NO:5 (CmnD), SEQ ID NO:6 (CmnE), SEQ ID NO:7 (CmnF), SEQ ID NO:8 (CmnG), SEQ ID NO:9 (CmnH), SEQ ID NO:10 (CmnI), SEQ ID NO:11 (CmnJ), SEQ ID NO:12 (CmnK), SEQ ID NO:13 (CmnL), SEQ ID NO:14 (CmnM), SEQ ID NO:15 (CmnN), SEQ ID NO:16 (CmnO), SEQ ID NO:17 (CmnP), SEQ ID NO:18 (CmnR), SEQ ID NO:19 (CmnU), and SEQ ID NO:20 (Cph).
An isolated and purified nucleic acid molecule that encodes a CmnA gene product having the amino acid sequence set forth in SEQ ID NO:2.
Dependencies are inferred from the claim text.