US 12,241,072 B2
Biosynthetic approach for heterologous production and diversification of bioactive lyciumin cyclic peptides
Roland D. Kersten, Arlington, MA (US); and Jing-Ke Weng, Belmont, MA (US)
Assigned to Whitehead Institute for Biomedical Research, Cambridge, MA (US)
Appl. No. 16/963,099
Filed by Whitehead Institute for Biomedical Research, Cambridge, MA (US)
PCT Filed Jan. 21, 2019, PCT No. PCT/US2019/014430
§ 371(c)(1), (2) Date Jul. 17, 2020,
PCT Pub. No. WO2019/144083, PCT Pub. Date Jul. 25, 2019.
Claims priority of provisional application 62/732,957, filed on Sep. 18, 2018.
Claims priority of provisional application 62/620,420, filed on Jan. 22, 2018.
Claims priority of provisional application 62/619,905, filed on Jan. 21, 2018.
Prior Publication US 2020/0347396 A1, Nov. 5, 2020
Int. Cl. C12N 15/82 (2006.01); C07K 7/64 (2006.01); C07K 14/415 (2006.01)
CPC C12N 15/8241 (2013.01) [C07K 7/64 (2013.01); C07K 14/415 (2013.01)] 26 Claims
 
1. A method of producing one or more lyciumin cyclic peptides, the method comprising:
a) providing a host cell comprising a transgene encoding a precursor peptide comprising: i) a signal peptide; ii) one or more peptide domains of eight amino acids comprising SEQ ID NO: 294; and iii) a BURP domain comprising two phenylalanine residues at its N-terminus, two cysteine residues, and four repeated cysteine-histidine motifs, arranged as SEQ ID NO: 282;
b) expressing the transgene in the host cell to thereby produce the precursor peptide, wherein the precursor peptide is converted to one or more lyciumin cyclic peptides in the host cell; and
c) isolating one or more of the lyciumin cyclic peptides from the host cell.